Dose-response studies with nitroso-1,2,3,6-tetrahydropyridine and dinitrosohomopiperazine in F344 rats

Dose-response studies were carried out on female F344 rats with two carcinogenic cyclic nitrosamines, nitroso-1,2,3,6-tetrahydropyridine (NTHP) and dinitrosohomopiperazine (DNHP). Groups of 20 rats were given the nitrosamines in drinking water solution, at concentrations ranging from 100 to 1 mg/liter of the former and 110 to 1.1 mg/liter of the latter, each lower dose being 40% of the dose above it. The lengths of treatment were 25 or 30 weeks at the higher concentrations, and were extended to most of the lifespan at the lower concentrations. The mortality rate of the animals with induced tumors of the upper gastrointestinal tract (and liver in the case of the highest dose of NTHP), decreased with lower doses at the higher concentrations. At the lower concentrations there was little effect on mortality rate, compared with untreated controls, but there were a number of rats with induced tumors of the upper GI tract and the incidence of these tumors increased with increasing dose of nitrosamine. Of the doses given, only the lowest dose of DNHP given for the shortest time was without significant carcinogenic effect. The relationship between dose of nitrosamine and carcinogenic potency, as measured by mortality rate, was linear over part of the range, but not at lower doses. The slopes of these dose responses differed between NTHP- and DNHP-treated animals, suggesting that the mechanisms of carcinogenesis by these two compounds are not identical.