Mutagenic activity of the 4,5- and 9,10-dihydrodiols of benzo[j]fluoranthene and their syn- and anti-dihydrodiol epoxides in Salmonella typhimurium.
The objective of this study was to determine the relative mutagenic activities of the major dihydrodiol metabolites of benzo[j]fluoranthene (B[j]F) and their corresponding syn- and anti-dihydrodiol epoxides. Salmonella typhimurium tester strains TA97a, TA98, and TA100 were used to evaluate the mutagenic potencies of the parent hydrocarbon and these suspect proximate and ultimate mutagenic metabolites. B[j]F and the trans-dihydrodiol metabolites were active only in the presence of an external metabolic activation system (S9) with the exception of the B[j]F-4,5-diol, which was weakly active in TA98 and TA100 in the absence of S9. The B[j]F-4,5-diol was more mutagenic than the B[j]F-9,10-diol in tester strains TA98 and TA100, whereas the opposite effect was observed in TA97a. In the absence of S9, the anti-B[j]F-4,5-diol epoxide was more mutagenic than the syn-B[j]F-4,5-diol epoxide and the syn- and anti-B[j]F-9,10-diol epoxides in tester strains TA97a and TA100. The exceptional mutagenic potency of the anti-B[j]F-4,5-diol epoxide in TA100 resembles that observed by epoxides located within a fjord, or by the anti-diol epoxides of bay region methylated polycyclic aromatic hydrocarbons. In contrast, the mutagenicity of the pseudo bay region dihydrodiol epoxides arising from the B[j]F-9,10-diol more closely resembles that observed with the classical bay region dihydrodiol epoxides of chrysene. In summary, both dihydrodiol metabolites of B[j]F are mutagenic in S. typhimurium, and the relative potency varies among the tester strains. The highest mutagenic response was achieved in tester strain TA100, which detects base-pair substitutions. The most potent direct-acting dihydrodiol epoxide in this tester strain was the anti-B[j]F-4,5-diol epoxide, which agrees with the results of mouse skin painting studies that indicate that the B[j]F-4,5-diol is more tumorigenic that the parent hydrocarbon or the B[j]F-9,10-diol. A covalent DNA adduct formed between the anti-B[j]F-4,5-diol epoxide and deoxyguanosine was the major species of DNA adduct formed in S. typhimurium. This adduct corresponds to the major DNA adduct formed in mouse skin following application B[j]F.
Marshall
M V
MV
Park One Research Laboratories, Sugar Land, Texas 77478.
He
Z M
ZM
Weyand
E H
EH
Rice
J E
JE
LaVoie
E J
EJ
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004852:Epoxy Compounds / Q000633:toxicity; D005449:Fluorenes / Q000737:chemistry / Q000633:toxicity*; D008862:Microsomes, Liver / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D013329:Structure-Activity Relationship
D004852:Epoxy Compounds; D005449:Fluorenes; D009153:Mutagens; C027704:benzo(j)fluoranthene