Structure-mutagenicity relationship in α,β-unsaturated carbonylic compounds and their corresponding allylic alcohols

Abstract

Several α,β-unsaturated carbonylic compounds and their corresponding allylic alcohols were tested in a modified Salmonella typhimurium mutagenicity assay according to Rannug et al. (1976) with and without metabolic activation by S9 mix. The mutagenic activities of the test substances were correlated with their chemical structures. Allyl alcohol exerted a significant direct mutagenic activity despite its lack of a good leaving (750 revertants/μmole). Glycidol, the epoxide of allyl alcohol, showed a lower direct mutagenic potential (80 revertants/μmole), whereas the corresponding aldehyde, acrolein, exhibited a direct mutagenicity 3 times higher than that of allyl alcohol. The possibility of an oxidation of allyl alcohol to its corresponding α,β-unsaturated carbonyl compound, acrolein, by bacterial alcohol dehydrogenase is discussed. The 3 methyl-substituted homologues of allyl alcohol, crotyl alcohol, 2-methallyl alcohol and 3-buten-2-ol, only showed borderline mutagenicity, while the higher homologs, 2-cyclohexen-1-ol, cinnamyl alcohol, geraniol and linalood, did not show any mutagenic properties. In contrasst with the methyl-substituted homologs of allyl alcohol, the methylated homologs of acrolein, croton aldehyde, 2-methylacrolein and methylvinyl ketone, were clearly mutagenic. Of the higher α,β-unsaturated carbonyl compounds tested in this study, only 2-cyclohexen-1-one, which has the lowest molecular weight, exerted a very small direct mutagenic effect, whereas cinnamylaldehyde and citral did not show any mutagenicity. The addition of S9 mix invariably led to a decrease in mutagenicity; this is most distinct with those compounds that had the highest direct mutagenic potential. The chemical reactivity of acrolein with deoxyadenosine was confirmed in an experiment in vitro.