Jerome J Solomon, Ph.D.

Cyclic adducts and intermediates induced by simple epoxides
Solomon JJ
1999 ;(150):123-135, IARC scientific publications (Lyon)
Simple epoxides such as ethylene oxide, propylene oxide, epichlorohydrin and glycidol are mutagenic and carcinogenic compounds that are important industrial chemicals. Mutagenic and carcinogenic epoxides can also be formed metabolically from Industrially important compounds such as alkenes (ethylene, butadiene, propylene and styrene), vinyl halides (vinyl chloride and vinyl bromide) and other vinyl monomers (acrylonitrile and acrylamide). Simple epoxides react with nucleosides and DNA predominantly by the SN2 mechanism at the most nucleophilic sites (ring nitrogens) in DNA to form 2-hydroxy-2-alkyl adducts. The major hydroxyalkyl adducts that form at N7 of deoxyguanosine and N3 of deoxyadenosine are chemically unstable owing to the presence of a charged quaternary nitrogen at the site of alkylation, and they depurinate spontaneously to remove the charge, forming potentially mutagenic abasic sites. Hydroxyalkylation at N1 of deoxyadenosine and N3 of deoxycytidine also results in the production of charged, unstable species because the pKa increases dramatically after alkylation. The charge can be lost from these adducts by the formation of cyclic adducts, which occurs when there is a good leaving group on the hydroxyalkyl side-chain. Most simple epoxides remove the charge on hydroxyalkyl adducts at N1 of deoxyadenosine and N3 of deoxyxytidine by competitive rearrangements, such as hydrolytic deamination, to form 1-hydroxyalkyl-deoxyinosine and 3-hydroxyalkyl-deoxyuridine adducts and Dimroth rearrangement to form N6-hydroxyalkyl-deoxyadenosine adducts. These rearrangements are facilitated intramolecularly by the formation of cyclic intermediates, with the participation of the hydroxyl group of the hydroxyalkyl side-chain. These adducts are uncharged, stable and potentially mutagenic and are likely to contribute to the biological activity of simple epoxides
— id: 10356, year: 1999, vol: , page: 123, stat: Journal Article,

3-Dihydroxypropyl-dU: A potentially mutagenic lesion produced by the epoxides epichlorohydrin and glycidol
Bhanot OS; Singh US; Solomon JJ
1997 ;38:A265-A265, Proceedings of the annual meeting of the American Association for Cancer Research
3-Hydroxyalkyl-dU lesions are produced by several aliphatic epoxides after initial alkylation at N3 of dC followed by rapid hydrolytic deamination. The mutagenic and carcinogenic epoxides epichlorohydrin (ECH) and glycidol (GLY) produce the same adduct 3-dihydroxypropyl-dU (3-DHP-dU). The mutagenic potential of 3-DHP-dU was investigated by in vitro DNA replication studies of this lesion placed at a single site in a DNA template. In the presence of the natural metal cofactor Mg++, 3-DHP-dU blocked DNA synthesis 3' to the lesion and after incorporating a nucleotide opposite 3-DHP-dU. Postlesion synthesis was negligible (1%). In the absence of polymerase proofreading activity, bypass (52%) at 3-DHP-dU occurred which was enhanced (91%) by substitution of Mg++ with Mn++. Sequencing revealed that dA and dT are incorporated opposite 3-DHP-dU during postlesion synthesis. Since 3-DHP-dU is derived from dC alkylation by ECH and GLY incorporation of dA and dT opposite 3-DHP-dU implicates this lesion in GC to AT and GC to TA mutagenesis by these epoxides. These results together with our DNA replication studies of ethylene oxide-induced 3-hydroxyethyl-dU and propylene oxide-induced 3-hydroxypropyl-dU suggest that 3-hydroxylalkyl-dU may be critical premutagenic lesions produced by these environmentally important epoxides
— id: 6026, year: 1997, vol: 38, page: A265, stat: Journal Article,

Reaction of epichlorohydrin with 2'-deoxynucleosides: characterization of adducts
Singh US; Decker-Samuelian K; Solomon JJ
1996 Jan 5;99(1-3):109-128, Chemico-biological interactions
Epichlorohydrin (ECH) is a simple 3-carbon epoxide of industrial importance and thus has the potential for human exposure in the workplace. It has been shown to be genotoxic in several systems and is a compound capable of reacting with biological nucleophiles. This study details the products formed from the reaction of ECH with 2'-deoxynucleosides at pH 7 and 37 degrees C for 6 h. Reaction with 2'-deoxyguanosine yielded 7-(3-chloro-2-hydroxypropyl) guanine (7-CHP-Gua) resulting from alkylation at N-7 of 2'-deoxyguanosine followed by depurination. Two unusual adducts were also partially characterized which resulted from further reaction of 7-CHP-Gua with another molecule of ECH to yield 1,7-bis(3-chloro-2-hydroxypropyl)guanine (1,7-bis-CHP-Gua) which could then cyclize with the exocyclic amino group to yield 1,N2-(2-hydroxypropano)-7-(3-chloro-2-hydroxypropyl) guanine (1,N2-HP-7-CHP-Gua). Reaction with 2'-deoxyadenosine gave only one product, namely 1,N6-(2-hydroxypropano)-2'-deoxyadenosine (1,N6-HP-dAdo). The reaction of 2'-deoxythymidine with ECH also yielded one product which was identified as 3-(3-chloro-2-hydroxypropyl)-2'-deoxythymidine (3-CHP-dThd). A 3-(3-chloro-2-hydroxypropyl)-2'-deoxyuridine (3-CHP-dUrd) product was isolated from the reaction of ECH with 2'-deoxycytidine. This product most likely resulted from the deamination of an initially formed 3-(3-chloro-2-hydroxypropyl) -2'-deoxycytidine (3-CHP-dCyd), a phenomenon which we have previously reported to occur during the reaction of 2'-deoxycytidine with other aliphatic epoxides. Evidence is also presented that 3-CHP-dUrd is converted to 3-(2,3-dihydroxypropyl)-2'deoxyuridine (3-DHP-dUrd) under physiological conditions, with a half-life of 213 h. Reaction of ECH with calf thymus DNA (pH 7.0, 37 degrees C, 3 h) resulted in the formation of 7-CHP-Gua (200 nmol/mg DNA
— id: 6963, year: 1996, vol: 99, page: 109, stat: Journal Article,

BIOLOGICAL SIGNIFICANCE OF EPOXIDE-INDUCED 3-HYDROXYALKYL-DEOXYURIDINE LESIONS IN DNA
SOLOMON, JJ; LAI, C; BHANOT, OS
1995 JAN 5 ;336(3):197-197, Journal of cellular biochemistry
— id: 87353, year: 1995, vol: 336, page: 197, stat: Journal Article,

The role of 3-hydroxyethyldeoxyuridine in mutagenesis by ethylene oxide
Bhanot OS; Singh US; Solomon JJ
1994 Nov 25;269(47):30056-30064, Journal of biological chemistry
Ethylene oxide, a direct-acting mutagen and carcinogen, produces 3-hydroxyethyldeoxyuridine (3-HE-dU) after initial alkylation at N3 of dC, followed by rapid hydrolytic deamination. The significance of formation of 3-HE-dU in DNA was investigated by in vitro DNA replication of 3-HE-dU. A 55-nucleotide DNA template, containing 3-HE-dU at a single site, was constructed. DNA products, synthesized on the site-modified template, were analyzed and mutagenic bypass at 3-HE-dU estimated. The 3-HE-dU lesion blocked DNA replication by the Klenow fragment of Escherichia coli polymerase I (Kf Pol I) and bacteriophage T7 polymerase (T7 Pol) 3' to 3-HE-dU and after incorporating a nucleotide opposite 3-HE-dU. DNA synthesis past 3-HE-dU was negligible (< 3%). Substitution of Kf Pol I (exo-) and T7 Pol (exo-), polymerases lacking 3'-->5' exonuclease proofreading activity, for Kf Pol I and T7 Pol, respectively, facilitated DNA synthesis past 3-HE-dU. The bypass synthesis by Kf Pol I (exo-) was 60% and 90% by T7 Pol (exo-). These results suggest that the 3-HE-dU lesion could be bypassed, but that the extension at 3-HE-dU is rate-limiting. In the absence of proofreading, the nucleotide incorporated opposite 3-HE-dU is not excised and remains in position long enough for extension to occur. During post-lesion synthesis, both dA and dT were incorporated opposite 3-HE-dU. Since 3-HE-dU is derived from dC alkylation by ethylene oxide, incorporation of dA and dT opposite 3-HE-dU implicates this lesion in G.C-->A.T and G.C-->T.A mutagenesis
— id: 6575, year: 1994, vol: 269, page: 30056, stat: Journal Article,

The role of mutagenic metal ions in mediating in vitro mispairing by alkylpyrimidines
Bhanot OS; Solomon JJ
1994 Sep;102 Suppl 3:81-90, Environmental health perspectives
A variety of alkylating mutagens and carcinogens produce pyrimidine adducts in DNA that block DNA synthesis in vitro. Since DNA synthesis past the lesion is a necessary step to produce mutations, we investigated the role of the mutagenic metal ion Mn++ in facilitating DNA synthesis past alkylpyrimidines. In the presence of the natural metal activator Mg++, N3-ethyldeoxythymidine (N3-Et-dT) and O2-ethyldeoxythymidine (O2-Et-dT), present at a single site in DNA, blocked in vitro DNA synthesis 3' to the lesion and after incorporating dA opposite each lesion. The presence of Mn++ permitted postlesion synthesis with dT misincorporated opposite N3-Et-dT and O2-Et-dT, implicating these lesions in A.T-->T.A transversion mutagenesis. The DNA synthesis block by O4-ethyldeoxythymidine (O4-Et-dT) in the presence of Mg++ was partial and was also removed by Mn++. Consistent with in vivo studies, dG was incorporated opposite O4-Et-dT during postlesion synthesis, leading to A.T-->G.C transition mutagenesis. We also have discovered a new class of DNA adducts, N3-hydroxyalkyldeoxyuridine (3-HA-dU) lesions, which are produced by mutagenic and carcinogenic aliphatic epoxides. 3-HA-dU is formed after initial alkylation at the N3 position of dC followed by a rapid hydrolytic deamination. As observed with the analogous mutagenic N3-Et-dT, the ethylene oxide-induced 3-hydroxyethyldeoxyuridine (3-HE-dU) blocked in vitro DNA synthesis, which could be by-passed in the presence of Mn++. The nucleotide incorporated opposite 3-HE-dU during postlesion synthesis is being identified. These studies suggest a role for Mn++ in mediating mutagenic and carcinogenic effects of environmentally important ethylating agents and aliphatic epoxides
— id: 6576, year: 1994, vol: 102 Suppl 3, page: 81, stat: Journal Article,

UVM, an ultraviolet-inducible RecA-independent mutagenic phenomenon in Escherichia coli
Palejwala VA; Pandya GA; Bhanot OS; Solomon JJ; Murphy HS; Dunman PM; Humayun MZ
1994 Nov 4;269(44):27433-27440, Journal of biological chemistry
Most mutagenic DNA lesions are noninstructive in the sense that template instruction is either missing or inaccessible during DNA replication, leading to replication arrest. According to the SOS hypothesis, arrested replication induces the expression of SOS factors that force replication past stalled sites at the cost of mutagenesis. We have recently shown that prior UV irradiation of delta recA cells, in which the SOS pathway does not function, enhances mutagenesis at an ethenocytosine residue borne on a circular gapped duplex DNA vector, indicating the existence of an SOS-independent inducible mutagenic phenomenon termed UVM (UV modulation of mutagenesis). In the previous experiments, mutation fixation was expected to occur during gap-filling DNA synthesis. To test whether UVM is observable during normal replication by DNA polymerase III, we have examined mutagenesis at an epsilon C residue borne on M13 single-stranded DNA. By analyzing mutation frequency and specificity using a multiplex sequence assay, we now show that UVM is observable in UV-irradiated recA+, and in delta recA cells. These data indicate that UV irradiation induces a previously unrecognized mutagenic mechanism in Escherichia coli, and that this mechanism is manifested during gap-filling DNA synthesis as well as during normal DNA replication
— id: 34558, year: 1994, vol: 269, page: 27433, stat: Journal Article,

Propylene oxide mutagenesis at template cytosine residues
Snow ET; Singh J; Koenig KL; Solomon JJ
1994 ;23(4):274-280, Environmental & molecular mutagenesis
Propylene oxide (PO) is a widely used industrial reagent which is mutagenic and carcinogenic. We have recently shown that a variety of aliphatic epoxides, including propylene oxide, can react with DNA to form hydroxyalkyl adducts at N-3 of cytosine which rapidly undergo hydrolytic deamination to produce uracil adducts. These 3-hydroxyalkyl uracil adducts are stable in DNA and are postulated to be an important class of potentially mutagenic lesions. Mutagenesis at cytosine residues due to PO modification of single-stranded M13mp2/C141 DNA was studied by transfection of modified DNA into SOS and non-SOS induced E. coli host cells. Mutations of the proline (CCC) codon at C141 which result in reversion of the lacZ phenotype (blue plaques) were scored. It was found that PO treatment of single-stranded DNA results in dose-dependent mutagenesis that is highly SOS dependent. The spectrum of base-substitution mutations found at this site differed when PO-modified DNA was transfected into E. coli with different DNA repair backgrounds. These results indicate that propylene oxide induced DNA adducts at template cytosine residues are mutagenic in E. coli and that this mutagenesis is greatly increased by SOS processing. They also show that these lesions may be repaired by one or more mechanisms
— id: 6522, year: 1994, vol: 23, page: 274, stat: Journal Article,

DNA adducts of lactones, sultones, acylating agents and acrylic compounds
Solomon JJ
1994 ;(125):179-198, IARC scientific publications (Lyon)
— id: 6752, year: 1994, vol: , page: 179, stat: Journal Article,

The extent and persistence of binding to respiratory mucosal DNA by inhaled tritiated propylene oxide
Snyder CA; Solomon JJ
1993 Aug 31;72(3):157-161, Cancer letters
In order to investigate some of the mechanisms underlying the carcinogenicity of inhaled propylene oxide (PO), the deposition and persistence of inhaled tritiated PO in the DNA of the nasal cavities, tracheae and lungs of rats were investigated. The results of dose/response exposure protocols revealed clear gradients for binding throughout the respiratory mucosa; the highest levels of binding were in the nasal mucosa and the lowest were in the lungs. Gradients became steeper as exposure concentrations were lowered. The persistence studies revealed that bound tritium declined in nasal mucosal DNA with apparent bi-exponential kinetics while clearance from the tracheal and pulmonary DNA was much slower and occurred with apparent mono-exponential kinetics. Consequently, although the initial levels of binding of inhaled PO are lower in the trachea and lungs than in the nasal cavity, the slow clearance of PO from the DNA in these organs could increase the chances of a mutational event
— id: 6523, year: 1993, vol: 72, page: 157, stat: Journal Article,

In vitro reactions of 2-cyanoethylene oxide with calf thymus DNA
Solomon JJ; Singh US; Segal A
1993 Sep;88(2-3):115-135, Chemico-biological interactions
2-cyanoethylene oxide (CEO) is a direct-acting mutagen and the postulated proximate carcinogenic form of acrylonitrile (AN). We have studied the reactions of CEO with 2'-deoxyribonucleosides and in vitro with calf thymus DNA at pH 7.0-7.5 and 37 degrees C for 3 h. Reaction of CEO with dAdo gave 2 adducts, N6-(2-hydroxy-2-carboxyethyl)-dAdo (N6-HOCE-dAdo) (2% yield) and 1,N6-etheno-dAdo (epsilon-dAdo) (11%); reaction with dCyd resulted in the isolation of 3-HOCE-dUrd (22%); reaction with dGuo gave 7-(2-oxoethyl)-Gua (7-OXE-Gua) (31%) and reaction with dThd yielded 3-OXE-dThd (3%). Structural elucidation of adducts was accomplished by ultraviolet spectroscopy, high-field proton NMR spectroscopy and mass spectrometry. Structural confirmation was provided by an accurate mass measurement technique where diagnostic ions in the electron impact mass spectra of trimethylsilyl derivatives were measured to within 0.0007 atomic mass units. The facile Dimroth rearrangement of 1-HOCE-dAdo to N6-HOCE-dAdo and hydrolytic deamination of a dCyd adduct to 3-HOCE-dUrd is postulated to be catalyzed by the hydroxyl group on the 3-carbon side chain of the adduct. Reaction of CEO with calf thymus DNA yielded (nmol/mg DNA) N6-HOCE-dAdo (2); epsilon-dAdo (11); 3-HOCE-dUrd (80); 7-OXE-Gua (110) and 3-OXE-dThd (1). Thus CEO, like its metabolic precursor AN, directly alkylates DNA in vitro but at a much more rapid rate
— id: 6524, year: 1993, vol: 88, page: 115, stat: Journal Article,

In vitro DNA replication implicates O2-ethyldeoxythymidine in transversion mutagenesis by ethylating agents
Bhanot OS; Grevatt PC; Donahue JM; Gabrielides CN; Solomon JJ
1992 Feb 11;20(3):587-594, Nucleic acids research
A 36-nucleotide oligomer containing a single O2-ethyldeoxythymidine (O2-Et-dT) adduct at a specific site was synthesized. The oligomer, which corresponds to a specific DNA sequence in gene G of bacteriophage phi X174, was used as a template by T7 DNA polymerase to investigate the in vitro mutagenic specificity of O2-Et-dT. At 10 microM dNTP and 5 mM Mg++, the progress of T7 DNA polymerase was interrupted by O2-Et-dT: 80% 3' to O2-Et-dT and 14% after incorporating a nucleotide opposite O2-Et-dT (incorporation-dependent blocked product). DNA synthesis past the lesion was low (6%). Incorporation of a nucleotide opposite O2-Et-dT and subsequent postlesion synthesis were enhanced by increasing the dNTP concentration, with postlesion synthesis reaching 30% at 200 microM. Postlesion synthesis was further increased to 45% by addition of 10 mM dAMP to the polymerization reactions. DNA sequencing revealed that both dA and dT were incorporated opposite O2-Et-dT with dA incorporation impeding the progress of DNA synthesis. dT incorporation was efficiently extended implicating O2-Et-dT in transversion mutagenesis in vivo. These studies provide a basis for understanding the molecular mechanisms by which ethylating agents contribute to cytotoxicity, A.T transversion mutagenesis and activation of the oncogene neu by an A.T----T.A transversion event in rat neuroblastomas
— id: 13693, year: 1992, vol: 20, page: 587, stat: Journal Article,

In vitro mispairing specificity of O2-ethylthymidine
Grevatt PC; Solomon JJ; Bhanot OS
1992 May 5;31(17):4181-4188, Biochemistry
The O2-position of thymine is a major site of base alkylation by N-nitroso-alkylating agents, and its biological relevance remains obscure. The potential significance of this DNA damage was ascertained by studying in vitro DNA replication properties of O2-ethylthymidine (O2-Et-dT) site-specifically incorporated into a 36-nucleotide template. DNA replication was initiated eight nucleotides away from the O2-Et-dT lesion by Escherichia coli polymerase I (Klenow fragment) using a 17-nucleotide primer. In the presence of 10 microM dNTP and Mg2+, O2-Et-dT blocked DNA replication predominantly (94%) 3' to O2-Et-dT, with the remainder (5%) blocked after incorporation of a nucleotide opposite O2-Et-dT (incorporation-dependent blocked product). Postlesion synthesis was negligible (less than 1%). Nucleotide incorporation opposite O2-Et-dT increased to 23% at 200 microM dNTP. Postlesion synthesis remained negligible (less than 2%). DNA sequencing revealed dA present opposite O2-Et-dT in the incorporation-dependent blocked product. Negligible postlesion synthesis suggests that incorporation of dA opposite O2-Et-dT inhibits in vitro DNA synthesis. The O2-Et-dT.dA base pair may also impede DNA synthesis in vivo, contributing to the cytotoxicity of the ethylating agents. Substitution of Mn2+ for Mg2+ enhanced nucleotide incorporation opposite O2-Et-dT and produced postlesion synthesis (16%) at 10 microM dNTP, which increased to 39% at 200 microM dNTP. DNA sequence analysis showed that while dA was present opposite O2-Et-dT in the incorporation-dependent blocked product, both dA and dT were present opposite this lesion in the postlesion synthesis product.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 8387, year: 1992, vol: 31, page: 4181, stat: Journal Article,

In vitro reaction of ethylene oxide with DNA and characterization of DNA adducts
Li F; Segal A; Solomon JJ
1992 Jun 15;83(1):35-54, Chemico-biological interactions
Ethylene oxide (EO) is a direct-acting SN2 alkylating agent and a rodent and probable human carcinogen. In vitro reactions of EO with calf thymus DNA in aqueous solution at neutral pH and 37 degrees C for 10 h resulted in the following 2-hydroxyethyl (HE) adducts (nmol/mg DNA): 7-HE-Gua (330), 3-HE-Ade (39), 1-HE-Ade (28), N6-HE-dAdo (6.2), 3-HE-Cyt (3.1), 3-HE-Ura (0.8) and 3-HE-dThd (2.0). Reference (marker) compounds were synthesized from reactions of EO with 2'-deoxyribonucleosides and DNA bases, isolated by paper and high performance liquid chromatography and characterized on the basis of chemical properties and UV, NMR and mass spectra. In agreement with our earlier studies with propylene oxide (PO) (Chem.-Biol. Interact., 67 (1988) 275-294) and glycidol (Cancer Biochem. Biophys., 11 (1990) 59-67), alkylation at N-3 of dCyd by EO under physiological conditions resulted in the rapid hydrolytic deamination of 3-HE-dCyd to 3-HE-dUrd. The hydroxyl group on the alkyl side chain which forms after epoxide alkylation is mechanistically involved in this rapid hydrolytic deamination. These results may provide important insights into the mechanisms of mutagenicity and carcinogenicity exhibited by EO and other SN2 aliphatic epoxides
— id: 13559, year: 1992, vol: 83, page: 35, stat: Journal Article,

Quantitative high-performance liquid chromatography analysis of DNA oxidized in vitro and in vivo
Frenkel K; Zhong ZJ; Wei HC; Karkoszka J; Patel U; Rashid K; Georgescu M; Solomon JJ
1991 Jul;196(1):126-136, Analytical biochemistry
Oxidative modification of genetic material has been implicated as a factor in carcinogenesis, particularly during promotion and progression, and therefore there is a need for sensitive detection of oxidized DNA bases. We developed a method that can be applied to DNA isolated from any source and used to simultaneously quantify oxidized nucleosides without a need to prelabel the DNA or use destructive hydrolytic procedures. This method is based on: (a) enzymatic DNA digestion; (b) HPLC separation of the resultant nucleosides; (c) acetylation of the oxidized nucleosides with [3H]Ac2O (acetic anhydride); (d) removal of the radioactive debris; and (e) quantitative analysis of tritiated nucleoside acetates by HPLC. Enzymatic DNA digestion was optimized using DNase I in the presence of Mg2+ (pH 7), followed by nuclease P1 in the presence of Zn2+ (pH 5.1) and alkaline phosphatase (pH 7.5). Analysis of DNA oxidized with H2O2 in the presence of Fe2+/EDTA for 30 min showed that the levels of 8-OHdG (8-hydroxy-2'-deoxyguanosine) were increased 2.7-fold, HMdU (5-hydroxymethyl-2'-deoxyuridine) 3.15-fold, and FdU (5-formyl-2'-deoxyuridine) 2.5-fold. Although the (-)-isomer of cis-dTG (cis-thymidine glycol) was enhanced 2.3 times, the (+)-isomer remained virtually unchanged. Analysis of DNA isolated from epidermal cells of mice treated in vivo with the tumor promoter TPA (12-O-tetradecanoylphorbol 13-acetate) showed 4.8-, 2.7-, and 8.7-fold increases in the levels of total cis-dTG, 8-OHdG, and HMdU, respectively, and of some unknown DNA oxidation products. These results prove applicability of the 3H-postlabeling method to the analysis of DNA (and potentially RNA) isolated from many sources, including animals and humans
— id: 13980, year: 1991, vol: 196, page: 126, stat: Journal Article,

Incorporation of dA opposite N3-ethylthymidine terminates in vitro DNA synthesis
Bhanot OS; Grevatt PC; Donahue JM; Gabrielides CN; Solomon JJ
1990 Nov 13;29(45):10357-10364, Biochemistry
N3-Ethylthymidine (N3-Et-dT) was site specifically incorporated into a 17-nucleotide oligomer to investigate the significance of DNA ethylation at the central hydrogen-bonding site (N3) of thymine. The 5'-(dimethoxytrityl)-protected N3-Et-dT was converted to the corresponding 3'-phosphoramidite and used to incorporate N3-Et-dT at a single site in the oligonucleotide during synthesis by the phosphite triester method. The purified N3-Et-dT-containing oligomer was ligated to a second 17-mer to yield a 34-nucleotide template with N3-Et-dT present at position 26 from the 3'-end. The template DNA, which corresponds to a specific sequence at gene G of bacteriophage phi X174, was used to study the specificity of nucleotide incorporation opposite N3-Et-dT. At 10 microM dNTP and 5 mM Mg2+, N3-Et-dT blocked DNA synthesis by Escherichia coli polymerase I (Klenow fragment): 96% immediately 3' to N3-Et-dT and 4% after incorporation of a nucleotide opposite N3-Et-dT (incorporation-dependent blocked product). DNA replication past the lesion (postlesion synthesis) was negligible. Incorporation opposite N3-Et-dT increased with increased dNTP concentrations, reaching 35% at 200 microM. Postlesion synthesis remained negligible. DNA sequencing of the incorporation-dependent blocked product revealed that dA is incorporated opposite N3-Et-dT consistent with the 'A' rule in mutagenesis. Formation of the N3-Et-dT.dA base pair at the 3'-end of the growing chain terminated DNA synthesis. These results implicate N3-Et-dT as a potentially cytotoxic lesion produced by ethylating agents
— id: 14276, year: 1990, vol: 29, page: 10357, stat: Journal Article,

In vitro reactions of isopropyl methanesulfonate with DNA and with 2'-deoxyribonucleosides
Li F; Solomon JJ; Mukai F; Segal A
1990 Nov;11(4):253-264, Cancer biochemistry biophysics
Isopropyl methanesulfonate (IPMS), an SN1 alkylating agent, is a direct-acting mutagen in bacteria. We recently reported that s.c. and topical administration of IPMS to mice resulted in the rapid induction of thymic lymphomas. Thymic lymphoma induction was not observed following administration of the SN2 alkylating agents methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS). We have studied the reactions of IPMS with dAdo, dCyd, dGuo and dThd at pH 6.5 to 7.5 and 37 degrees C for 3 h. IPMS formed the following isopropyl (IP) adducts: 7-IP-Gua (4% yield), O6-IP-Gua (8%), O2-IP-Cyt (1%), O2-IP-dThd (2%), 3-IP-dThd (1%), and O4-IP-dThd (0.4%). Adducts were characterized from UV and mass spectra. IPMS was reacted in vitro with calf thymus DNA (pH 6.5 to 7.5, 37 degrees C, 3 h) and yielded (nmol/mg DNA): 7-IP-Gua (22) O6-IP-dGuo (11), O2-IP-Cyt (9), O2-IP-dThd (2), O4-IP-dThd (2), 3-IP-Ade (0.2) and 3-IP-dThd (0.2). The relatively greater alkylation of exocyclic oxygen atoms in DNA by IPMS compared to values for MMS and EMS reported by others, may play a role in the induction of thymic lymphomas in mice by IPMS and the lack of such activity by MMS and EMS
— id: 14308, year: 1990, vol: 11, page: 253, stat: Journal Article,

INVITRO REACTIONS OF GLYCIDOL WITH PYRIMIDINE-BASES IN CALF THYMUS DNA
Segal, A; Solomon, JJ; Mukai, F
1990 Feb;11(1):59-67, Cancer biochemistry biophysics
— id: 32110, year: 1990, vol: 11, page: 59, stat: Journal Article,

Inhibition of soybean lipoxygenase and mouse skin tumor promotion by onion and garlic components
Belman S; Solomon J; Segal A; Block E; Barany G
1989 Fall;4(3):151-160, Journal of biochemical toxicology
Onion and garlic essential oils were previously shown to inhibit mouse skin tumor promotion, as were the enzymes, lipoxygenase, and cyclooxygenase. In the present study, the inhibition of soybean lipoxygenase (EC 1.13.11.12) by onion and garlic components and related compounds was investigated. The IC50 values as well as the kinetic inhibition constants were determined for the most active compounds. Di-(1-propenyl) sulfide, an analog of the substrate moiety required for oxygenase action, was the only irreversible inhibitor observed with Ki = 59 microM and k3 = 0.53/min. Inhibition in the presence of substrate was uncompetitive at 88 and 132 microM linoleic acid with Ki = 129 microM. At 173 microM linoleic acid, however, inhibition was competitive with Ki = 66 microM. Dially trisulfide, allyl methyl trisulfide, and diallyl disulfide were competitive inhibitors, while 1-propenylpropyl sulfide and (E, Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide (ajoene) were mixed inhibitors. Nordihydroguaiaretic acid (NDGA), the most potent lipoxygenase inhibitor, was a competitive inhibitor with Ki = 0.29 microM. The results indicate a relative potency of inhibition for structural features in the following order: di(1-propenyl) sulfide greater than an alkenyl trisulfide greater than an alkenyl disulfide. Di(n-propyl) disulfide, a major onion oil component, inhibited neither lipoxygenase nor promotion. Di(1-propenyl) sulfide and ajoene inhibited both. This suggests that the inhibition of lipoxygenase may be involved in antipromotion
— id: 10841, year: 1989, vol: 4, page: 151, stat: Journal Article,

Isolation of methylcarbamoyl-adducts of adenine and cytosine following in vitro reaction of methyl isocyanate with calf thymus DNA
Segal A; Solomon JJ; Li FJ
1989 ;69(4):359-372, Chemico-biological interactions
Methylisocyanate (MIC) is the direct-acting acylating compound involved in the Bhopal, India disaster which occurred on December 3rd, 1984. The accidental release of MIC resulted in at least 2000 deaths, thousands of injuries and exposure of at least 200,000 people to varying amounts of MIC. We have studied how MIC reacts with 2'-deoxyribonucleosides at pH 7.0 and 37 degrees C for 1 h. MIC acylates exocyclic amino groups resulting in the following methylcarbamoyl (MC) adducts: N6-MC-Ade (0.5% yield) and N4-MC-dCyd (6%). No adducts were detected with dThd and dGuo. UV, NMR and mass spectrometry were employed to spectroscopically characterize these adducts. MIC was reacted with calf thymus DNA (pH 7.0, 37 degrees C, 1 h) and yielded N6-MC-Ade (0.3 nmol/mg DNA) and N4-MC-dCyd (2.0 nmol/mg DNA). The inability of others to observe genetic mutations by MIC in Salmonella and Drosophila is consistent with the exocyclic adducts at N4 of Cyt and N6 of Ade where normal hydrogen bonding can occur after rotation of the methylcarbamoyl group anti to the Watson-Crick side of the molecule assuming that MIC binds to DNA within the intact cell
— id: 10771, year: 1989, vol: 69, page: 359, stat: Journal Article,

DNA adducts of propylene oxide and acrylonitrile epoxide: hydrolytic deamination of 3-alkyl-dCyd to 3-alkyl-dUrd
Solomon JJ; Segal A
1989 May;81:19-22, Environmental health perspectives
Propylene oxide (PO) and acrylonitrile epoxide (ANO) are 3-carbon epoxides that are direct-acting mutagens. PO is a rodent carcinogen, and ANO has been postulated to be the ultimate carcinogenic form of acrylonitrile (AN). We have studied the reactions of these agents with 2'-deoxynucleosides and in vitro with calf thymus DNA at pH 7.0 to 7.5 and 37 degrees C. PO was reacted with DNA for 10 hr and resulted in the formation of the following 2-hydroxypropyl (HP) adducts: N6-HP-dAdo (1 nmole/mg DNA), 3-HP-Ade (14 nmole/mg DNA), 7-HP-Gua (133 nmole/mg DNA) and 3-HP-dUrd (13 nmole/mg DNA). 3-HP-dUrd was formed after initial alkylation at N-3 of dCyd followed by conversion of the adjacent exocyclic imino group at C-4 to an oxygen (hydrolytic deamination) with the formation of a dUrd adduct. ANO was reacted for 3 hr with calf thymus DNA and yielded N6-(2-hydroxy-2-carboxyethyl-dAdo (N6-HOCE-dAdo) (2 nmole/mg DNA); 1, N6-etheno-dAdo (11 nmole/mg DNA); 7-(2-oxoethyl)-Gua (7-OXE-Gua) (110 nmole/mg DNA); 3-OXE-dThd (1 nmole/mg DNA); and 3-HOCE-dUrd (80 nmole/mg DNA). As with 3-HP-dUrd, 3-HOCE-dUrd resulted from hydrolytic deamination of an initially formed dCyd adduct. A mechanism is proposed for the conversion of 3-alkyl-dCyd to 3-alkyl-dUrd involving intramolecular catalysis by the OH group on the 3-carbon side chain of the adduct.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 10626, year: 1989, vol: 81, page: 19, stat: Journal Article,

Mechanism of H-ras oncogene activation in mouse squamous carcinoma induced by an alkylating agent
Hochwalt AE; Solomon JJ; Garte SJ
1988 Feb 1;48(3):556-558, Cancer research
A mouse skin squamous cell carcinoma induced by topical application of the direct-acting alkylating agent beta-propiolactone contains an activated H-ras oncogene with an A----T transversion at the second nucleotide of codon 61. The mutation was detected in NIH3T3 transfectant and original tumor DNA by an XbaI restriction enzyme polymorphism and confirmed by oligonucleotide 'mismatch' hybridization. The mutation was not seen in the liver of the same animal. The activated oncogene also exhibited several restriction enzyme polymorphisms in transfectant DNA due to a reciprocal translocation 3' to the coding region of the gene, which occurred during transfection. The activating mutation was found in only 1 of 6 beta-propiolactone induced mouse skin tumors examined, the only tumor with a transforming H-ras oncogene. This is a much lower frequency of activation than that previously reported for the same tumor type induced by polycyclic aromatic hydrocarbons. The A----T transversion mutation is consistent with a potentially direct mutagenic effect of a specific beta-propiolactone-DNA adduct
— id: 11202, year: 1988, vol: 48, page: 556, stat: Journal Article,

ADDUCTS CHARACTERIZED FOLLOWING INVITRO REACTION OF ACRYLONITRILE OXIDE (ANO) WITH CALF THYMUS DNA
Segal, A; Solomon, JJ; Mukai, F
1988 Mar;29(5):96-96, Proceedings (American Association for Cancer Research)
— id: 31479, year: 1988, vol: 29, page: 96, stat: Journal Article,

Reactions of propylene oxide with 2'-deoxynucleosides and in vitro with calf thymus DNA
Solomon JJ; Mukai F; Fedyk J; Segal A
1988 ;67(3-4):275-294, Chemico-biological interactions
Propylene oxide (PO) is a direct-acting mutagen and rodent carcinogen. We have studied how PO modifies 2'-deoxynucleosides at pH 7.0-7.5 and 37 degrees C for 10 h. PO reacts as an SN2 alkylating agent by forming the following 2-hydroxypropyl (HP) adducts: N6-HP-dAdo (7% yield), 7-HP-Gua (37%) and 3-HP-dThd (4%). Alkylation at N-3 of dCyd resulted in conversion of the adjacent exocyclic imino group at C-4 to an oxygen (hydrolytic deamination) with the formation of a dUrd adduct, 3-HP-dUrd (14%). Ultraviolet spectroscopy and mass spectrometry were used for the structural determination of these adducts. Confirmation of the unexpected 3-HP-dUrd adduct was provided by an accurate mass measurement technique where diagnostic ions in the mass spectra of 3-HP-dUrd were measured to within 0.0005 atomic mass units of the predicted mass. PO was reacted in vitro with calf thymus DNA (pH 7.0-7.5, 37 degrees C, 10 h) and yielded N6-HP-dAdo (1 nmol/mg DNA), 3-HP-Ade (14 nmol/mg DNA), 7-HP-Gua (133 nmol/mg DNA) and 3-HP-dUrd (13 nmol/mg DNA). A mechanism for the hydrolytic deamination of 3-HP-dCyd to 3-HP-dUrd involving the OH on the HP side chain is proposed. This cytosine to uracil conversion may play a role in the mutagenic and carcinogenic activity of this epoxide
— id: 11251, year: 1988, vol: 67, page: 275, stat: Journal Article,

INVITRO REACTION OF PROPYLENE-OXIDE WITH CALF THYMUS DNA - ALKYLATION AT N-3 OF CYTOSINE RESULTS IN CONVERSION TO A URACIL ADDUCT
Solomon, JJ; Fedyk, J; Mukai, F; Segal, A
1987 Mar;28(3):93-93, Proceedings (American Association for Cancer Research)
— id: 31216, year: 1987, vol: 28, page: 93, stat: Journal Article,

A simple mathematical model for diffusional sampler operation
Palmes, E D; Burton, R M Jr; Ravishankar, K; Solomon, J J
1986 Jul;47(7):418-420, American Industrial Hygiene Association journal
A simple mathematical model of the molecular basis for the function of a diffusional sampler for dilute mixtures of gaseous contaminants in supporting gases is presented. The model is based on the movement of single molecules of the contaminant between sections of a tubular diffusion path on a step-by-step basis; the length of the step and of each section of the tube are equal to the mean free path, lambda, under the specified conditions. When the model is used, the coefficient of diffusion, D, can be calculated from lambda and the average velocity, v, of the contaminant molecule. Both lambda and v were calculated independently using equations which involved the minimum number of assumptions. The value of D so estimated was of the same order as that in the literature, differing by a factor of less than 2. It should be emphasized that the model represents a statistical, thermodynamic approach to understanding diffusional samplers, and its utility is independent of the means of estimating lambda and v for specific gas pairs
— id: 106652, year: 1986, vol: 47, page: 418, stat: Journal Article,

CARCINOGENIC POTENCY OF DNA ADDUCTS
Albert, R; Snyder, C; Garte, S; Segal, A; Solomon, J
1985 ;26(MAR):87-87, Proceedings (American Association for Cancer Research)
— id: 30890, year: 1985, vol: 26, page: 87, stat: Journal Article,

Quantitative determination of the 5-(hydroxymethyl)uracil moiety in the DNA of gamma-irradiated cells
Frenkel K; Cummings A; Solomon J; Cadet J; Steinberg JJ; Teebor GW
1985 Aug 13;24(17):4527-4533, Biochemistry
5-(Hydroxymethyl)uracil (HMUra) is a chemically stable derivative of thymine formed through the action of ionizing radiation which we previously identified in the DNA of gamma-irradiated HeLa cells [Teebor, G. W., Frenkel, K., & Goldstein, M. S. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 318-321]. In this report, we determine whether HMUra can be used as a marker of exposure of DNA to ionizing radiation. Dose-response curves for its formation in [3H]thymidine-labeled DNA were constructed by exposing the DNA to increasing amounts of gamma-radiation and measuring the HMUra content. DNA was irradiated both in solution and in intact cells. HMUra was identified as the 2'-deoxyribonucleoside 5-(hydroxymethyl)-2'-deoxyuridine (HMdU) by subjecting the irradiated DNA to enzymatic digestion and analyzing the mixture of 2'-deoxyribonucleosides by high-pressure liquid chromatography. The identity of the radiogenically formed HMdU was confirmed by acetylation and the structure of the acetyl derivative obtained by mass and nuclear magnetic resonance spectroscopies. At two different DNA concentrations in solution, the same number of thymidine moieties were converted to HMdU, indicating that within this range of concentration the formation of HMdU was mediated through the indirect action of ionizing radiation. Equal amounts of HMdU were formed in single- and double-stranded DNA at each radiation dose, indicating that DNA conformation did not affect HMdU formation. Surprisingly, the G value (number of HMdU molecules formed/100 eV) was higher in irradiated cellular DNA than in DNA irradiated in solution.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 34055, year: 1985, vol: 24, page: 4527, stat: Journal Article,

Carcinogenicity of formaldehyde and hydrogen chloride in rats
Sellakumar, A R; Snyder, C A; Solomon, J J; Albert, R E
1985 Dec;81(3 Pt 1):401-406, Toxicology & applied pharmacology
Previous studies in this laboratory have shown that the combined exposure of hydrogen chloride (HCI) and formaldehyde vapors (HCHO) elicited a significant incidence of nasal cancer in rats. In studies performed elsewhere, it has been demonstrated that exposure to formaldehyde alone induced a high nasal cancer response in rats. We wished to determine whether concurrent exposure of hydrogen chloride would enhance the tumorigenic effects of formaldehyde. Two exposure techniques were used. In one hydrogen chloride and formaldehyde were premixed at high concentrations before entry into the exposure chambers in order to maximize the formation of reactive alkylating agents. In the second the hydrogen chloride and formaldehyde were introduced separately into the exposure chamber. Appropriate control exposures consisting of formaldehyde alone or hydrogen chloride alone or air alone were also performed. The results show that nasal cancer incidences were induced in all animals receiving HCHO regardless of concurrent exposure to hydrogen chloride. The tumors were predominantly squamous cell type arising from the anterior portion of the nasal cavity. This study demonstrates that hydrogen chloride does not appreciably influence the nasal carcinogenicity of formaldehyde
— id: 123135, year: 1985, vol: 81, page: 401, stat: Journal Article,

DIRECT ALKYLATION OF 2'-DEOXYNUCLEOSIDES AND DNA FOLLOWING INVITRO REACTION WITH ACRYLAMIDE
SOLOMON, JJ; FEDYK, J; MUKAI, F; SEGAL, A
1985 ;45(8):3465-3470, Cancer research
— id: 41148, year: 1985, vol: 45, page: 3465, stat: Journal Article,

DIRECT ALKYLATION OF CALF THYMUS DNA BY ACRYLONITRILE - ISOLATION OF CYANOETHYL ADDUCTS OF GUANINE AND THYMINE AND CARBOXYETHYL ADDUCTS OF ADENINE AND CYTOSINE
SOLOMON, JJ; SEGAL, A
1985 ;62(OCT):227-230, Environmental health perspectives
— id: 41181, year: 1985, vol: 62, page: 227, stat: Journal Article,

DNA ADDUCT FORMATION IN THE RAT NASAL-MUCOSA BY DIRECT-ACTING CARCINOGENS
ALBERT, RE; SNYDER, C; GARTE, S; GOLDSCHMIDT, B; SOLOMON, J; SEGAL, A
1984 ;25(MAR):88-88, Proceedings (American Association for Cancer Research)
— id: 40958, year: 1984, vol: 25, page: 88, stat: Journal Article,

5-HYDROXYMETHYL URACIL (HMU) IS A MARKER OF RADIATION-DAMAGE TO DNA
FRENKEL, K; CUMMINGS, A; CADE, J; SOLOMON, J; TEEBOR, GW
1984 ;25(MAR):105-105, Proceedings (American Association for Cancer Research)
— id: 40959, year: 1984, vol: 25, page: 105, stat: Journal Article,

ACRYLONITRILE REACTS WITH 2'-DEOXYNUCLEOSIDES AND INVITRO WITH CALF THYMUS DNA TO FORM CYANOETHYL ADDUCTS WITH GUA AND THY AND CARBOXYETHYL ADDUCTS WITH ADE AND CYT - AN AUTOCATALYZED HYDROLYSIS IS POSTULATED FOR CONVERSION OF THE NITRILE MOIETY TO A CARBOXYLIC-ACID
Segal, A; Solomon, JJ
1984 ;188(AUG):143-143, Abstracts of papers (American Chemical Society)
— id: 30995, year: 1984, vol: 188, page: 143, stat: Journal Article,

ACRYLONITRILE REACTS WITH 2'-DEOXYNUCLEOSIDES AND INVITRO WITH CALF THYMUS DNA TO FORM CYANOETHYL ADDUCTS WITH GUA AND THY AND CARBOXYETHYL ADDUCTS WITH ADE AND CYT - AN AUTOCATALYZED HYDROLYSIS IS POSTULATED FOR CONVERSION OF THE NITRILE MOIETY TO A CARBOXYLIC-ACID
SEGAL, A; SOLOMON, JJ
1984 ;23(14):3373-3373, Biochemistry
— id: 40942, year: 1984, vol: 23, page: 3373, stat: Journal Article,

INVITRO ALKYLATION OF CALF THYMUS DNA BY ACRYLONITRILE - ISOLATION OF CYANOETHYL-ADDUCTS OF GUANINE AND THYMINE AND CARBOXYETHYL-ADDUCTS OF ADENINE AND CYTOSINE
SOLOMON, JJ; COTE, IL; WORTMAN, M; DECKER, K; SEGAL, A
1984 ;51(2):167-190, Chemico-biological interactions
— id: 40782, year: 1984, vol: 51, page: 167, stat: Journal Article,

ACRYLONITRILE (AN) REACTS INVITRO WITH CALF THYMUS DNA TO FORM CYANOETHYL (CNE)-ADDUCTS WITH GUA AND THY AND CARBOXYETHYL (CE)-ADDUCTS WITH ADE AND CYT
SOLOMON, JJ; COTE, IL; WORTMAN, MJ; DECKER, K; SEGAL, A
1984 ;25(MAR):83-83, Proceedings (American Association for Cancer Research)
— id: 40957, year: 1984, vol: 25, page: 83, stat: Journal Article,

N-nitroso compounds: evidence for their presence in airborne particles
Kneip, T J; Daisey, J M; Solomon, J J; Hershman, R J
1983 Sep 9;221(4615):1045-1047, Science
Chemical, infrared, and thermal energy analyses have provided evidence for the presence of the N-nitroso functional group in extracts of airborne particles. The total molar N-nitroso concentrations in New York City air are equivalent to the total concentrations of polycyclic aromatic hydrocarbons. Since 90 percent of the N-nitroso compounds that have been tested are carcinogens, the newly discovered but untested materials may represent a significant environmental hazard
— id: 68690, year: 1983, vol: 221, page: 1045, stat: Journal Article,

Formation of N⁴-dimethyl-5-methyl-2'-deoxyoytidine following in vitro reaction of dimethylcarbamyl
Segal A; Mate U; Solomon JJ; Van Duuren BL
1982 ;13:98-98, Abstracts of papers (International Union against Cancer)
— id: 58762, year: 1982, vol: 13, page: 98, stat: Journal Article,

Formation of 6-dimethylcarbamyloxy-dGuo, 6-dimethylamino-dGuo and 4-dimethylamino-dThd following in vitro reaction of dimethylcarbamyl chloride with calf thymus DNA and 6-diethylcarbamyloxy-dGuo following in vitro reaction of diethylcarbamyl chloride with calf thymus DNA
Segal A; Solomon JJ; Mate U; Van Duuren BL
1982 Jun;40(2):209-231, Chemico-biological interactions
The rodent carcinogens dimethylcarbamyl chloride (DMCC) and diethylcarbamyl chloride (DECC) react with dGuo (pH 7.0-7.5, 37 degrees C, 4 h) to form the O6-acyl derivatives 6-dimethylcarbamyloxy-2'-deoxyguanosine (6-DMC-dGuo) and 6-diethylcarbamyloxy-2'-deoxyguanosine (6-DEC-dGuo), respectively. Reaction of DMCC with dThd under identical conditions yielded 4-dimethylamino-thymidine (4-DMA-dThd). Compounds 6-DMC-dGuo and 6-DEC-dGuo undergo a nucleophilic aromatic substitution reaction with dimethylamine (DMA) to form 6-dimethylamino-2'-deoxyguanosine (6-DMA-dGuo) via displacement of the C-6 dialkylcarbamyloxy moiety. The substitution reaction did not take place when diethylamine or NH3 were substituted for DMA. The structures of the new compounds 6-DMC-dGuo, 6-DEC-dGuo, 4-DMA-dThd and 6-DMA-dGuo were deduced from chemical analyses and syntheses, UV and nuclear magnetic resonance (NMR) spectra and electron impact, isobutane chemical ionization and source insertion isobutane chemical ionization mass spectra. It was postulated that 4-DMA-dThd was formed following reaction of the transient intermediate 4-DMC-dThd with DMA formed by hydrolysis of DMCC. Calf thymus DNA was reacted in vitro with DMCC (pH 7.0-7.5, 37 degrees C, 4 h) and the modified DNA hydrolyzed enzymatically to 2'-deoxynucleosides. Compounds 6-DMC-dGuo, 4-DMA-dThd and 6-DMA-dGuo were identified in the hydrolysate by high-pressure liquid chromatography (HPLC). In an identical manner 6-DEC-dGuo was identified following in vitro reaction of DECC with calf thymus DNA. Compounds 6-DEC-dGuo and 6-DMC-dGuo possess novel structures with respect to the types of adducts known to be formed between carcinogens and bases in DNA. The implications of these findings with respect to chemical mutagenesis and carcinogenesis is discussed. The structural relationship between N4-dimethyl-5-methylcytosine (4-dimethylamino-Thy) formed in DNA following in vitro reaction with DMCC and 5-methylcytosine, the only modified base found in vertebrate DNA is noted
— id: 57994, year: 1982, vol: 40, page: 209, stat: Journal Article,

Loss of essential membrane lipids and ascorbic acid from rat brain following cryogenic injury and protection by methylprednisolone
Mitamura JA; Seligman ML; Solomon JJ; Flamm ES; Demopoulos HB; Ransohoff J
1981 ;3(4):329-344, Neurological research
Previous work has shown that unsaturated fatty acid components of model membrane phospholipids in vitro, damaged via a free radical mechanism, are protected by the presence of cholesterol in these membranes. The participation of these membrane lipids in the pathogenesis of traumatic injury to brain was studied in vivo using the Klatzo method of cryogenic injury in rats. Increased edema 4 hr after cryogenic injury was noted on the lesioned side. Total cerebral cholesterol was decreased significantly in the lesioned hemispheres 10 hr following injury. In lesioned animals pretreated and post-treated with methylprednisolone, there were no significant differences in the cholesterol levels. Arachidonic acid isolated from total membrane phospholipids was significantly reduced on the injured side 24 hr after injury, but not before. Other fatty acids were not significantly affected. Methylprednisolone treatment prevented the decrease in arachidonic acid. Animals that had received a cold injury had significant decreases in ascorbic acid levels after 4 hr on the lesioned side of the brain. This decrease was significantly ameliorated by corticosteroid administration. These results support the hypothesis that the protective effect of corticosteroids in cryogenic cerebral trauma may be due to antioxidant protection of major cell membrane lipid components such as cholesterol and phospholipids
— id: 28964, year: 1981, vol: 3, page: 329, stat: Journal Article,

FORMATION OF O6-ACYL GUANINE DERIVATIVES FOLLOWING INVITRO REACTIONS BETWEEN DIMETHYLCARBAMYL AND DIETHYLCARBAMYL CHLORIDE WITH CALF THYMUS DNA
SEGAL, A; MATE, U; SOLOMON, JJ; VANDUUREN, BL
1981 ;22(MAR):84-84, Proceedings (American Association for Cancer Research)
— id: 40180, year: 1981, vol: 22, page: 84, stat: Journal Article,

THE ISOLATION AND CHARACTERIZATION OF 3-(2- CARBOXYETHYL)CYTOSINE FOLLOWING INVITRO REACTION OF BETA- PROPIOLACTONE WITH CALF THYMUS DNA
Segal, A; Solomon, JJ; Mignano, J; Dino, J
1981 ;35(3):349-361, Chemico-biological interactions
— id: 30207, year: 1981, vol: 35, page: 349, stat: Journal Article,

A novel nucleophilic aromatic substitution of acyloxy goup at O⁶ of deooxyguanosine
Solomon JJ; Segal A; Van Duuren BL; Mate U
1981 ;29:750-750, Annual Conference on Mass Spectrometry & Allied Topics
— id: 58783, year: 1981, vol: 29, page: 750, stat: Journal Article,

REACTION OF EPOXIDES WITH 4-NITROTHIOPHENOL - ITS POSSIBLE APPLICATION FOR TRAPPING AND CHARACTERIZATION OF EPOXIDES
Agarwal, SC; Vanduuren, BL; Solomon, JJ; Kline, SA
1980 ;14(10):1249-1253, Environmental science & technology
— id: 27896, year: 1980, vol: 14, page: 1249, stat: Journal Article,

ISOLATION OF 3-(2-CARBOXYETHYL)THYMINE FOLLOWING INVITRO REACTION OF BETA-PROPIOLACTONE WITH CALF THYMUS DNA
Segal, A; Solomon, JJ; Mate, U
1980 ;29(3):335-346, Chemico-biological interactions
— id: 28074, year: 1980, vol: 29, page: 335, stat: Journal Article,

FORMATION OF 3-(2-CARBOXYETHYL) THYMINE FOLLOWING INVITRO REACTION BETWEEN BETA-PROPIOLACTONE AND CALF THYMUS DNA
Segal, A; Mate, U; Solomon, JJ
1979 ;20(MAR):3-3, Proceedings (American Association for Cancer Research)
— id: 30097, year: 1979, vol: 20, page: 3, stat: Journal Article,

INVITRO DIMROTH REARRANGEMENT OF 1-(2-CARBOXYETHYL) ADENINE TO N6-(2-CARBOXYETHYL)-ADENINE IN SINGLE-STRANDED CALF THYMUS DNA
Segal, A; Mate, U; Solomon, JJ
1979 ;28(2-3):333-344, Chemico-biological interactions
— id: 28079, year: 1979, vol: 28, page: 333, stat: Journal Article,

Mass spectrometry and reactivity of chloroalkene epoxides
Solomon JJ; Van Duuren BL; Kline SA
1979 ;27:639-639, Annual Conference on Mass Spectrometry & Allied Topics
— id: 58784, year: 1979, vol: 27, page: 639, stat: Journal Article,

SYNTHESIS AND REACTIONS OF CHLOROALKENE EPOXIDES
Kline, SA; Solomon, JJ; Vanduuren, BL
1978 ;43(18):3596-3600, Journal of organic chemistry
— id: 29672, year: 1978, vol: 43, page: 3596, stat: Journal Article,

Tumor-promoting activity of 2,3-dihydrophorbol myristate acetate and phorbolol myristate acetate in mouse skin
Segal A; Van Duuren BL; Mate U; Solomon JJ; Seidman I; Smith A; Melchionne S
1978 Apr;38(4):921-925, Cancer research
Phorbolol myristate acetate (PHMA) had been previously prepared from the potent mouse skin tumor promoter phorbol myristate acetate (PMA) by sodium borohydride reduction of the C-5 carbonyl group in PMA to a secondary alcohol. PHMA was shown to have an inflammatory effect in mouse skin equal to that of PMA. 2,3-Dihydrophorbol myristate acetate (DPMA), a new compound, was prepared from the 3-aldehyde of PMA by catalytic hydrogenation. DPMA exhibited no detectable inflammatory effect in mouse skin. Both DPMA and PHMA were tested on the dorsal skins of female ICR/Ha Swiss mice (30/group) for 433 and 380 days, respectively, in separate experiments. The tumor-promoting activity of both compounds was reduced significantly, compared with that of equimolar doses of PMA. For each treatment the number of mice with tumors per total number of tumors was: DPMA, 9/17; PMA, 29/553 at 10 microgram/mouse; PMA, 30/317; PHMA, 24/69 at 2.5 microgram/mouse. The results suggest that specific binding requirements influence the tumor-promoting and hyperplastic activity of PMA and its closely related derivatives in mouse skin
— id: 58006, year: 1978, vol: 38, page: 921, stat: Journal Article,

Chemical ionization mass spectrometry of the tumor promoter related 4aalpha-phorbol esters
Solomon JJ; Van Duuren BL; Tseng SS
1978 Feb;5(2):164-169, Biomedical mass spectrometry
The isobutane chemical ionization mass spectra of a series of 4aalpha-phorbol esters have been determined. Phorbol myristate acetate, a diester of phorbol, is the most potent known tumor promoter in mouse skin carcinogenesis. Several esters of the stereoisomer of phorbol have been synthesized to study the effect of structure and stereochemistry on tumor promotion. Conventional electron impact mass spectra of these esters gave little or no molecular weight information due to their low volatility, tendency to dehydrate and complex fragmentation to peaks in the low mass end of the spectrum. Isobutane chemical ionization mass spectrometry greatly enhanced the molecular ion region and through functional group selectivity established the identity of the various substituted esters
— id: 58009, year: 1978, vol: 5, page: 164, stat: Journal Article,

INVITRO BINDING OF BETA-PROPIOLACTONE TO CALF THYMUS DNA AND MOUSE-LIVER DNA TO FORM 1-(2-CARBOXYETHYL)ADENINE
Mate, U; Solomon, JJ; Segal, A
1977 ;18(3):327-336, Chemico-biological interactions
— id: 29522, year: 1977, vol: 18, page: 327, stat: Journal Article,

Chemical ionization mass spectrometry of phorbol esters
Solomon JJ; Tseng S-S; Van Duuren BL
1977 ;25:622-622, Annual Conference on Mass Spectrometry & Allied Topics
— id: 58785, year: 1977, vol: 25, page: 622, stat: Journal Article,

Synthesis of 4aalpha-phorbol 9-myristate 9a-acetate and related esters
Tseng SS; Van Duuren BL; Solomon JJ
1977 Nov 11;42(23):3645-3649, Journal of organic chemistry
— id: 58012, year: 1977, vol: 42, page: 3645, stat: Journal Article,