Bovine bladder and liver cell and homogenate-mediated mutagenesis of Salmonella typhimurium with aromatic amines.
Comparisons of aromatic amine activation were made by using intact cells or cell homogenates (S-9) from bovine bladder urothelium and liver. Since both liver and bladder are thought to contribute carcinogenic metabolites for bladder cancer initiation, comparisons of these two organs' relative ability to activate aromatic amines to mutagens were made. Salmonella typhimurium mutagenesis was used as an indication of mutagen production. Activation occurred in a dose dependent manner and no mutagenic response occurred unless activating cells or S-9 were present. Bladder urothelial cells metabolically activated the carcinogens, 2-amino-fluorene (AF), 2-acetylaminofluorene (AAF), 4-aminobiphenyl (4ABP), benzidine (BZ), and 2-naphthylamine (2NA) but not 1-naphythylamine (1NA), a non-carcinogen. Liver cells were less active than bladder cells in activating AF and AAF; but there was little or no hepatocyte activation of 4ABP, BZ, 2NA and 1NA. Intact bladder cells were more effective than bladder S-9 in activating AAF, but not in activating AF, 4ABP, BZ and 2NA. The liver S-9 showed more mutagenic activity with AF than did intact liver cells; the reverse was true for AAF, and bovine liver S-9 showed little or no activation of 4ABP, BZ, and 2NA. 1NA was not activated by either S-9 preparation. As was the case for intact cells, bladder S-9 was more effective than liver S-9 in activating the aromatic amines studied. The results demonstrate the capacity of bovine bladder urothelium to metabolically activate aromatic amines and suggest a role for the target organ itself in carcinogen activation. Information on the relative usefulness of intact cells versus S-9 preparations as activation systems was also obtained from these studies.
D000588:Amines / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D002417:Cattle; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects*; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000378:metabolism*
D000588:Amines; D002273:Carcinogens; D009153:Mutagens