An intestinal cell-mediated chromosome aberration test for the detection of genotoxic agents.
The use of rat-liver S9 in genotoxicity tests may not reflect true metabolism by whole cells, particularly cells of target organs. We have tested mucosal cells of the mouse small intestine for the capacity to mediate activation/inactivation of chemical carcinogens. Mucosal cells were isolated by pronase digestion. Three million cells were co-cultured with Chinese hamster ovary fibroblasts during a 3-h exposure to chemical clastogens. In the presence of the mucosal cells, aflatoxin B1 (100 microM) was activated to produce chromosome aberrations in 30% of Chinese hamster ovary cell metaphases. 4-Nitroquinoline 1-oxide was deactivated by intestinal cells, while benzo[a]pyrene and dimethylbenz[a]anthracene were not activated by the cells. The clastogenicity of the phenolic compounds caffeic acid (0.28 mg/ml) and clorogenic acid (0.25 mg/ml) was eliminated by the mouse intestinal preparation. The pyrrolizidine alkaloid monocrotaline was activated by intestinal cells. The results suggest the presence of specific activation and deactivation enzymes in the intestinal mucosa. The intestine cell-mediated chromosome aberration test could provide a means to measure tissue-specific activation and deactivation capabilities.
D015112:4-Nitroquinoline-1-oxide / Q000378:metabolism; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism; D001711:Biotransformation; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity; D009154:Mutation; D010053:Ovary; D051381:Rats
D001580:Benzopyrenes; D009153:Mutagens; D001564:Benzo(a)pyrene; D015112:4-Nitroquinoline-1-oxide; D015127:9,10-Dimethyl-1,2-benzanthracene