Biomedical subjects

E A Messerly

Publications and source records attributed to E A Messerly.

6 recordsLinked to original sources

PubMed1990

DNA strand breaks in liver for four aliphatic epoxides in mice.

Four aliphatic epoxides, 1-naphthyl glycidyl ether (NGE), 1-naphthylpropylene oxide (NPO), 4-nitrophenyl glycidyl ether (NPGE), 3,3,3-trichloropropylene oxide (TCPO) and two of their precursors, 1-allylnaphthalene (AN) and 3,3,3-trichloropropylene (TCP), were selected for DNA strand-break analysis in liver in vivo with mice. The four epoxides selected were among the most mutagenic aliphatic epoxides in our previous structure-mutagenicity studies with the Ames test and had been evaluated for their in vivo genotoxicity as measured by sister-chromatid exchange (SCE) and chromosome aberrations (CA). A significant increase in the percentage of unwound DNA was observed at a 4-h exposure time for all the compounds at high doses except for AN. TCPO, the least genotoxic compound in bone marrow, had the greatest liver toxicity after 1-h exposure while NGE showed the most toxicity after 6 h. As might be expected from their corresponding epoxides, AN but not TCP exhibited significant SCE activity in the bone marrow of mice. This study reemphasizes the importance of evaluating the stability of direct-acting alkylating agents in comparing test results and in establishing the relative order of genotoxicity for such compounds.

Animals↗

PubMed1989

Mutagenicity of oxaspiro compounds with Salmonella.

The spiro attachment of an epoxide group to a tetrahydropyran ring in the trichothecene mycotoxins has prompted this study of the mutagenicity and alkylation rates of the trichothecene, anguidine, and 5 related model oxaspiro compounds. While the model compounds were weak alkylating agents of 4-(4-nitrobenzyl)pyridine as a test nucleophile, anguidine lacks such activity. Also, while mutagenicity was not established for anguidine in Salmonella TA100, 3 of the oxaspiro compounds were weakly mutagenic and 2 compounds were toxic to the bacteria. The toxicity and mutagenicity of the model compounds are more related to their polarity than to their alkylation rates.

Alkylating Agents↗

PubMed1989

Sister-chromatid exchange and chromosome aberrations for 4 aliphatic epoxides in mice.

Sister-chromatid exchange (SCE) and chromosome aberrations (CA) in bone marrow cells were analyzed after in vivo exposure in mice to 4 aliphatic epoxides, namely 1-naphthyl glycidyl ether (NGE), 1-naphthyl propylene oxide (NPO), 4-nitrophenyl glycidyl ether (NPGE) and trichloropropylene oxide (TCPO). These compounds were selected as being among the most mutagenic aliphatic epoxides in our previous structure-mutagenicity studies with the Ames test. There were significant dose-related increases in SCE and CA results for all 4 epoxides. The order of genotoxicity as established through SCE was NGE greater than NPO greater than NPGE approximately equal to TCPO greater than solvent control. It is of interest that Ames Salmonella results are consistent with in vivo genotoxicity for these compounds. However, only the plate test version of the Ames procedure is consistent with this order of in vivo genotoxicity and neither preincubation Ames testing results nor chemical alkylation rates would have predicted this order.

Animals↗

PubMed1989

Mutagenicity in Salmonella and sister chromatid exchange in mice for the bay-region syn- and anti-diol epoxides of 1,4-dimethylphenanthrene.

Dose-response relationships for (+/-)-7 alpha,8 beta-dihydroxy-5 beta,6 beta-epoxy-1,4-dimethyl-5,6,7,8-tetrahydrophenanthrene and its 5 alpha,6 alpha-epoxy diastereomer, the syn- and anti-diol epoxides of 1,4-dimethylphenanthrene respectively, have been established for their mutagenicity in Salmonella strains TA98 and TA100 and for their in vivo sister chromatid exchange in the bone-marrow cells of mice. Both isomers were mutagenic in the eta mole per plate range with the syn isomer being in the order of fifteen times more active with TA98 and five times more mutagenic in TA100 than its anti isomer. The anti isomer was more genotoxic in the sister chromatid exchange assay than the syn isomer. Statistically significant results were obtained as low as 1.5 mg/kg body weight for the anti isomer and 3 mg/kg for the syn isomer. The present study supports the inclusion of methyl-substituted bay-region diol epoxides in the concept that the syn isomer, with quasi-diequatorial hydroxyl groups, can contribute to the genotoxicity of the parent polycyclic aromatic hydrocarbons of those compounds which form hindered bay-region diol epoxides.

Animals↗

PubMed1988

Mutagenicity of aromatic glycidyl ethers with Salmonella.

6 aromatic glycidyl ethers containing naphthyl, biphenyl or benzylphenyl substituents were synthesized. These epoxides together with the commercially available compounds 2-biphenylyl glycidyl ether were examined for dose-mutagenicity relationships using the plate incorporation Ames test with Salmonella typhimurium strains TA100 and TA1535. Structure-mutagenicity relationships were further examined for these compounds and 3 phenyl glycidyl ethers by concurrent testing at a single dose with strain TA100. Meaningful correlations could not be established for the mutagenicity of these epoxides to their molecular volumes, partition values, nor to their reactivities with the model nucleophile, 4-(4-nitrobenzyl) pyridine. However, it was noted that increased conjugated aromatic unsaturation with its resulting planarity led to increased mutagenicity and that this effect decreased when it was further removed from the epoxide moiety.

Alkylation↗

PubMed1987

Structure-mutagenicity relationships of benzidine analogues.

The mutagenic activities of benzidine, its dihydrochloride salt, and 12 of their analogues were compared in the Ames test using strains TA100 and TA98 with and without rat liver S9 activation. With the exceptions of 4,4'-methylenebis(3-nitroaniline) in both strains and 3,3-dichlorobenzidine in TA98, little or no mutagenicity was observed in the series when tested without S9 activation. All compounds, except tetramethylbenzidine, exhibited some activity in TA100 with S9 activation; dichlorobenzidine and 4-aminobiphenyl were significantly more mutagenic than the other compounds. This was in contrast to the TA98 results where the bridged diphenyl compounds, with the exception of the nitroaniline derivative, were only slightly mutagenic compared to the more planar biphenyl series. Only the nitroaniline compound was mutagenic in both strains in the presence or absence of S9 activation. For benzidine and the 3,3'-disubstituted benzidines (the dimethoxy-, diamino-, and dichloro- compounds), an increase in mutagenicity correlated to a decrease in basicity of the parent anilines in both TA100 and TA98.

Animals↗