Mutagenicities of styrene oxide derivatives on bacterial test systems: relationship between mutagenic potencies and chemical reactivity.
The reaction products of deoxyguanosine with 3,4-dimethyl-, p-methyl-, m-methyl-, m-methoxy-, p-bromo-, m-chloro- and unsubstituted styrene oxide were isolated and characterized. The reaction followed second-order kinetics. The reactive site was the N-7 site of guanine. The normal isomer (attack at CH2 of styrene oxides) and the abnormal isomer (attack at CH) were obtained. The Hammett reaction constant (rho) for the normal reaction was +0.42 and that for the abnormal reaction was -1.1. The difference of acid dissociation constant, rate of imidazole ring opening and rate of glycosidic bond cleavage was not found between the normal adduct and the abnormal adduct. Styrene oxides have been tested for toxicity and mutation in a liquid suspension assay using Escherichia coli WP2 and some of its repair deficient derivatives. Salmonella typhimurium TA100 was also employed. The mutation frequency of 3,4-dimethylstyrene oxide was higher in CM571 than in WP2. The greatest mutability was found with the WP2uvrA strain. 3,4-Dimethylstyrene oxide also acted as an inducer of E. coli K-12 (kappa). The mutagenicity of 3,4-dimethylstyrene oxide may depend on a combination of the recA-dependent and recA-independent action mechanisms. The mutagenicities of these compounds in WP2uvrA and TA100 increased in the order: m-chlorostyrene oxide = p-bromostyrene oxide less than m-methoxystyrene oxide less than styrene oxide less than m-methylstyrene oxide less than p-methylstyrene oxide less than 3,4-dimethylstyrene oxide. There was no correlation between the mutagenicities and the total reaction rates. On the other hand, the reaction rates of these compounds for the abnormal reaction correlated with their mutagenicities. The results indicate that the mutagenic effect of a chemical is not dependent simply on the quantity of the adducts, but may vary with structure of its adducts.
D010582:Bacteriophage lambda / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003849:Deoxyguanosine; D004852:Epoxy Compounds / Q000633:toxicity*; D004926:Escherichia coli / Q000187:drug effects; D004988:Ethers, Cyclic / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship; D014775:Virus Activation / Q000187:drug effects
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D009153:Mutagens; C013690:styrene oxide; D003849:Deoxyguanosine