Mutagenicity of aromatic glycidyl ethers with Salmonella

Abstract

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.

Potential of the NBP Method for the Study of Alkylation Mechanisms: NBP as a DNA-Model

“…32,44,45,67,175−177 Several explanations for this lack of consistency have been advanced: (i) a higher competition by solvolysis in the case of more reactive compounds; 119 (ii) differences in selectivity toward N and O nucleophiles; 1,142 (iii) differences in the mutagenic events arising from O6 and N7 lesions; 119 (iv) the mutagenic test system used was not appropriate; 67 (v) interference by other reactions, e.g., in the case of N-methyl-N′-alkyl-N-nitrosoureas, the effective alkylating agent is formed during the decomposition of nitrosoureas; 178 and (vi) mutagenicity is influenced more intensely than alkylating activity by properties such as polarity, 45 molecular volume, 44 or the degree of unsaturation of aryloxides 177 or glycidyl oxides. 176 Whereas chemical carcinogens exert their effects through many different mechanisms, the NBP test has also been found to be a good predictor of the carcinogenicity and in vivo genotoxicity of alkylating agents (Table 5).…”

“…This assumption may work within classes of compounds, but attention must be paid to substituents that have strong effects on chromophores, such as carbonyl or diazo groups, and conjugated π systems, such as allyl or aryl groups. Intergroup correlation, however, is often poor, , and discrepancies in response among different classes of compound have been reported. ,,,,− …”

Base‐pair mutations caused by six aliphatic epoxides in salmonella typhimurium TA100, TA104, TA4001, and TA4006

“…In an extension of our interest in structure-mutagenicity relationships of aliphatic epoxides [Wade et al, 1978;Neau et al, 1982;Djuric et al, 1986;Rosman et al, 1986Rosman et al, , 1987Rosman et al, , 1988. we wished to characterize base-pair mutations in model epoxides by phenotypic screening.…”