Comparison of induction of DNA single-strand breaks and initiation of rat hepatocarcinogenesis by different nitrosamines.

The capacities of nitrosamines to induce DNA single-strand breaks (SSB) and to initiate carcinogenesis in rat liver were compared. N-Nitrosodiethanolamine (NDELA), N-nitrosoethylhydroxyethylamine (NEHEA) and N-nitrosodiethylamine (NDEA) were equipotent in inducing DNA SSB when administered by gavage at doses of 0.35 mmol/kg, 0.015 mmol/kg and 0.37 mmol/kg, respectively. Male Wistar rats were injected with these nitrosamines and were then submitted to a selection procedure. Ten rats per group were sacrificed one week after the end of the selection to see the effects of the nitrosamines on the development of preneoplastic lesions. The numbers of gamma-glutamyl transferase (GGT)-positive lesions per cm2 were 0.8, 2.1, 5.2 and 40.1 in rats treated with saline, NDELA, NEHEA and NDEA, respectively. N-Nitrosobis(2,2,2-trifluorethyl)amine (6F-NDEA), a nongenotoxic and noncarcinogenic nitrosamine, induced 0.7 GGT-positive lesions per cm2. Ten rats per group also received 0.05% phenobarbital in their drinking-water and were killed six months after initiation in order to see the effect of the different nitrosamines on the incidence and yield of tumours. Two extrahepatic cancers were found after administration of NEHEA, whereas two hepatocellular carcinomas were detected after injection of NDEA. No cancer developed in the other groups. Although other factors may influence the process, these results indicate that no simple correlation can be established between induction of SSB in DNA and initiation of tumours by nitrosamines in rat liver.