The mutagenicity of dibenz [a,h]anthracene activated by phenobarbital-inducible mouse-liver mono-oxygenase is potentiated by the presence of hydrophilic residues at the K-region of the molecule.
Dibenz[a,h]anthracene and synthetic K-region derivatives of the parent hydrocarbon and of benz[a]anthracene were tested for mutagenicity by the reversion of histidine-dependent Salmonella typhimurium TA98, TA100 and TA1537. The K-region metabolite 5,6-dihydroxy-5,6-dihydrodibenz[a,h]anthracene, inactive as such, was efficiently activated to mutagens for TA98 and TA100 by mouse-liver 9000 X g supernatant or microsomal fraction. Microsomes from phenobarbital- or Aroclor-1254-treated mice were efficient for this activation, while those from untreated or beta-naphthoflavone-treated mice were much less active. A study on the influence of various structural features on this efficient activation by phenobarbital-inducible mono-oxygenase of mouse-liver microsomes showed that, if the K-region were saturated, no metabolism to mutagens occurred, while substitution of the K-region by carbonyl and hydroxyl substituents led to increased mutagenic efficacy with increasing hydrophilicity (dihydro less than carbonyl less than hydroxyl). The K-region epoxide was the only derivative that did not require metabolic activation and it had a markedly different mutagenic specificity in that it was also mutagenic for TA1537.
D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism / Q000494:pharmacology*; D001711:Biotransformation; D004790:Enzyme Induction; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D010634:Phenobarbital / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects; D013045:Species Specificity
D001551:Benz(a)Anthracenes; D009153:Mutagens; D006899:Mixed Function Oxygenases; C026486:1,2,5,6-dibenzanthracene; D010634:Phenobarbital