Metabolism of 2-aminoanthracene by BALB/c and C57BL mammary epithelium in vitro.
Aromatic primary amines, activated by P-450-dependent mixed-function oxidases have been shown to be mutagenic and carcinogenic in mammary gland of rodents. In this study, we compared 2-aminoanthracene (2AA) metabolism and inhibition in primary mammary gland cultures of BALB/c and C57BL mice. We sought to establish whether the rate or extent of metabolism was strain dependent as observed with polycyclic aromatic hydrocarbons even though the metabolic process would be different. Cells from either strain of mouse were uninjured by doses of 2AA up to 20 microM but produced polar metabolites of 2AA, some of which apparently formed covalent bonds with cellular macromolecules. In each case, covalent binding was inhibited by alpha-napthoflavone (alpha-NF), a mixed-function oxidase inhibitor. Any notable strain differences in 2AA metabolism and disposition was not observed. Results indicate that mouse mammary epithelial cells are capable of producing reactive metabolites of 2AA, probably via mixed-function oxidation. Thus, metabolic activation of 2AA in breast tissue may induce mutagenesis in mammary epithelium. The inhibitory effects of alpha-NF suggest that this compound may be of interest as a potential anti-carcinogen for the mammary gland.
D000818:Animals; D000873:Anthracenes / Q000378:metabolism* / Q000633:toxicity; D002273:Carcinogens / Q000378:metabolism*; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism; D005260:Female; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013045:Species Specificity
D000873:Anthracenes; D002273:Carcinogens; C006593:2-anthramine