Reduced DNA repair response of carcinogen-induced hyperplastic cells in rat urinary bladder exposed to N-methyl-N'-nitro-N-nitrosoguanidine in organ culture.

DNA repair response to N-methyl-N'-nitro-N-nitrosoguadine (MNNG) was examined in an organ culture of hyperplastic urinary bladder epithelium, induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male F344 rats. Organ cultures of urinary bladders obtained from rats given a solution of 0.05% BBN for 4-12 weeks, were processed and exposed to MNNG (10(-3)M). The DNA repair response was estimated by autoradiographic analysis of unscheduled DNA synthesis (UDS). In general, hyperplastic cells of the urinary bladder induced by BBN showed lower UDS levels than those of non-hyperplastic cells. The reduction of DNA repair response to MNNG was more prominent in advanced hyperplastic cells with longer BBN treatment than in early appearing hyperplastic cells with shorter BBN treatment.