A comparative approach to 7, 12-dimethylbenz[a]anthracene effects: Metabolism and mutagenesis in mice and fish
- National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)
- Environmental Protection Agency, Narragansett, RI (United States)
A comparative approach was used to examine the effects of exposure to the potent carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) in two divergent sentinel species, mouse and fish, containing a common transgenic reporter, the bacteriophage {O}X174am3. Effects of DMBA were examined using both in vitro and in vivo studies through the analysis of metabolites, cytochrome P450 was examined 72 hours after DMBA dosing using an assay for 7-ethoxyresorufin-o-deethylase (EROD) activity. Fish showed an increasing trend of EROD induction with increasing dose, with the EROD level at the highest dose being significantly greater than corn oil controls and the lowest DMBA dose. DMBA had less of an effect on mouse P450 levels. Metabolites of DMBA in the bile at 12 hours were quantified in both species using HPLC/PDA detection. Bile extracts were enzyme digested to differentiate glucuronide, sulfate and glutathione conjugates. Primary metabolites in mice were 2-hydroxy-7,12-dimethylbenz[a]anthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene. The same metabolites were detected in the fish with the addition of 7,12-bis-hydrodxymethylbenz[a]anthracene. In vitro assays using uninduced and 3-methylcholanthrene-induced mouse microsomes showed no increase over background mutant frequencies of 1-3x10{sup -6} when 0X DNA was incubated with DMBA. In vivo induced mutation was also examined in mice and fish liver. The 1.9 and 19 mg/kg doses of DMBA resulted in a 10-fold increase in mutation frequency over controls in fish. There was a similar increase in mutation frequency at the 19 mg/kg dose in mice. Analysis of the 1.9 mb/kg dosed mice and the replicate variance among treated and control animals is underway.
- OSTI ID:
- 530835
- Report Number(s):
- CONF-9704100-; ISSN 0893-6692; TRN: 97:003016-0008
- Journal Information:
- Environmental and Molecular Mutagenesis, Vol. 29, Issue Suppl.28; Conference: 28. annual meeting of the Environmental Mutagen Society, Minneapolis, MN (United States), 19-23 Apr 1997; Other Information: PBD: 1997
- Country of Publication:
- United States
- Language:
- English
Similar Records
Identification of 7,12-dimethylbenz(a)anthracene metabolites that lead to mutagenesis in mammalian cells
Metabolism of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene in cultured human fetal aortic smooth muscle cells