Formation of mutagenic metabolites from benzo(a)pyrene and 2-aminoanthracene by the s-9 fraction from the liver of the Northern pike (Esox lucius): inducibility with 3-methylcholanthrene and correlation with benzo[a]pyrene monooxygenase activity.
The mutagenicity of benzo[a]pyrene and 2-aminoanthracene in the Ames test using the S-9 fraction from the liver of the Northern pike (Esox lucius) was tested. S-9 fractions were prepared both from fish injected intraperitoneally with 3-methylcholanthrene and from control animals. In addition benzo[a]pyrene monooxygenase activity was assayed in the same S-9 fractions used in the Ames test. S-9 fractions from the liver of the Northern pike were found to convert benzo[a]pyrene and 2-aminoanthracene to mutagenic metabolites. The number of revertants obtained was increased 2--4-fold in the case of 2-aminoanthracene and 3--14-fold in the case of benzo[a]pyrene by pretreatment of the pike with a single intraperitoneal injection of 3-methylcholanthrene. This injection also caused a 2--6-fold increase in the benzo[a]pyrene monooxygenase activity of the S-9 fractions used. These increases in mutagenicity and activity of the S-9 fractions used. these increases in mutagenicity and activity occur mainly during the first 4--12 days after the injection, but further small increases are observed for as long as 60 days. A strong positive correlation was found between the benzo[a]pyrene monooxygenase activity of the S-9 fractions used and their ability to give rise to revertants in the Ames test using 2-aminoanthracene or benzo[a]pyrene. This indicates that the major determining factor in the production of reactive metabolites which attack DNA in this in vitro system is the activity of the phase I cytochrome P-450 system.
D000818:Animals; D000873:Anthracenes / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001564:Benzo(a)pyrene; D001579:Benzopyrene Hydroxylase / Q000378:metabolism*; D001580:Benzopyrenes / Q000378:metabolism*; D001711:Biotransformation; D005260:Female; D005399:Fishes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects; D013997:Time Factors
D000873:Anthracenes; D001580:Benzopyrenes; D009153:Mutagens; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; C006593:2-anthramine; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases