Activation and detoxication of promutagens by toadfish (Opsanus tau) hepatic postmitochondrial fractions in the Salmonella assay.
Three groups of experiments were conducted to characterize the hepatic postmitochondrial fraction (S9) from the oyster toadfish (Opsanus tau) as an activation system for promutagens in the Salmonella assay and to provide an initial evaluation of the extent to which data from standard in vitro assays with mammalian activation systems are predictive of possible genotoxic effects in this marine fish. In the first group of experiments the effects of increasing the concentration of S9 from untreated and 3-methylcholanthrene (MC)- or Aroclor 1254 (AC)-pretreated toadfish and Sprague-Dawley rats on the mutagenicities of different concentrations of 2-aminoanthracene (2AA) and benzo[a]pyrene (BAP) were examined in Salmonella (TA98) plate assays. The maximum levels of 2AA mutagenicity attained by S9 from untreated (UI S9) toadfish and rats were comparable, but UI S9 from toadfish was more effective than UI S9 from rats in mediating BAP mutagenicity. MC pretreatment decreased maximum levels of 2AA mutagenicity and increased maximum levels of BAP mutagenicity mediated by S9 from both species. MC pretreatment also altered the pattern of dependence of 2AA mutagenicity on the concentration of S9 protein for S9 from both species. A similar alteration in the pattern of dependence of BAP mutagenicity on the concentration of S9 protein was also observed with S9 from MC-pretreated toadfish. Although AC pretreatment of rats effected changes in the mutagenicities of both test chemicals similar to those effected by MC pretreatment, AC pretreatment of toadfish effected little or no change in the mutagenicities of either test chemical. The changes in the pattern of dependence of 2AA and BAP mutagenicities on the concentration of S9 protein effected by MC pretreatment of toadfish were confirmed in a separate group of experiments. A third group of experiments was designed to examine the effects of alpha-naphthoflavone (ANF) on the mutagenicities of 2AA and BAP mediated by UI and MC S9 from toadfish. Although ANF did not affect the 2AA mutagenicity mediated by UI S9, a significant decrease in 2AA mutagenicity and a significant increase in BAP mutagenicity mediated by MC S9 and a significant decrease in BAP mutagenicity mediated by UI S9 were observed. These results indicate that 2AA and BAP are effectively activated by toadfish S9 and that, as in rats, these two test chemicals are activated and/or detoxicated by different cytochrome P-450-dependent pathways. These results also support the contention that cytochrome P-450-dependent detoxication pathways can be an important determinant of the mutagenic potency of some promutagens in vitro.
D000818:Animals; D000873:Anthracenes / Q000378:metabolism; D001140:Aroclors / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000378:metabolism; D001571:Benzoflavones / Q000494:pharmacology; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D005399:Fishes / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects
D000873:Anthracenes; D001140:Aroclors; D001571:Benzoflavones; D009153:Mutagens; D001564:Benzo(a)pyrene; C011512:alpha-naphthoflavone; C006593:2-anthramine