Bacterial mutagenicity of new cyclopenta-fused cata-annelated polycyclic aromatic hydrocarbons, and identification of the major metabolites of benz[j]acephenanthrylene formed by Aroclor-treated rat liver microsomes.
Three novel cyclopenta-fused polycyclic aromatic hydrocarbons were synthesized, benz[d]aceanthrylene, benz[k]aceanthrylene, and benz[j]acephenanthrylene, and evaluated for mutagenic activity in the Ames Salmonella typhimurium plate incorporation assay. The two benzaceanthrylene derivatives were active at low S9 concentrations in strain TA98 (4 and 27 rev/nmole respectively), as had been predicted from the calculated delta Edeloc/beta values of the carbocations derived from opening of the cyclopenta-fused epoxide rings, but the majority of this mutagenicity appeared to be due to free-radical decomposition products of spontaneous endo-peroxide formation. These compounds were therefore not further investigated. Benz[j]acephenanthrylene was also an indirect-acting frameshift mutagen (8-12 rev/nmole in strain TA98), but unlike most of the previously assayed cyclopenta-fused polycyclic aromatic hydrocarbons exhibited no peak of activity at low S9 protein concentration. The principal metabolites formed from this compound by microsomes from Aroclor-treated rat liver were benz[j]acephenanthrylene-4,5-dihydro-4,5-diol (necessarily derived from hydration of benz[j]acephenanthrylene 4,5-oxide) and benz[j]acephenanthrylene-9,10-dihydro-9,10-diol (precursor to benz[j]acephenanthrylene-9,10-dihydrodiol 7,8-oxide, the bay-region diol-epoxide). Consideration of the reduced activity of this compound compared to the related structure chrysene, the S9 dependence curves, and the predicted delta Edeloc/beta values of the postulate active species, suggests that in contrast to most other cyclopenta-fused polycyclic aromatic hydrocarbons, bay-region diol-epoxide formation plays a greater role than epoxidation of the cyclopenta-fused ring in the metabolic activation of benz[j]acephenanthrylene.
Ball
L M
LM
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill 27599.
Warren
S H
SH
Sangaiah
R
R
Nesnow
S
S
Gold
A
A
D000818:Animals; D001140:Aroclors / Q000633:toxicity; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008748:Methylcholanthrene / Q000031:analogs & derivatives* / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D011083:Polycyclic Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics*; D013056:Spectrophotometry, Ultraviolet
D001140:Aroclors; D011083:Polycyclic Compounds; D008748:Methylcholanthrene; C037411:benz(j)aceanthrylene