Induction of unscheduled DNA synthesis in primary culture of dog, rat, and mouse urothelial cells by arylamine and nitrofuran derivatives.
The induction of unscheduled DNA synthesis in primary cultures of urothelial cells from rats, mice, and dogs by nitrofurans and arylamines and their derivatives was examined. Electron microscopy of the culture from rat cells showed the characteristics of epithelial cells. The cultured cells were exposed to the test chemicals in a serum-free medium containing 10 mM hydroxyurea and [3H]thymidine for 24 hr, and unscheduled DNA synthesis was determined by autoradiography. N-Hydroxy-2-aminofluorene, N-hydroxy-2-acetylaminofluorene, N-hydroxy-4-amino-biphenyl, and N-hydroxy-4-acetylaminobiphenyl were active in inducing unscheduled DNA synthesis in the urothelial cells of rats, mice, and dogs. 2-Aminofluorene, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, and 2-amino-4-(5-nitro-2-furyl)thiazole were active only in dog cells. 2-Acetylaminofluorene and 4-aminobiphenyl were not active. These results demonstrate that urothelial cells contain enzymes that can selectively activate bladder carcinogens and their metabolites.
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005449:Fluorenes / Q000494:pharmacology; D051379:Mice; D009581:Nitrofurans / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000588:Amines; D005449:Fluorenes; D009581:Nitrofurans