Hydrazine is carcinogenic to the mouse and rat, but three earlier studies have reported no carcinogenicity of
hydrazine in the hamster. Administration of
hydrazine to mice, rats and hamsters results in rapid methylation of liver
DNA guanine for which endogenous
formaldehyde appears to be the source of the methyl moiety. Hamsters were given
hydrazine sulfate at 170, 340 and 510 mg/l in the
drinking water for 2 years [average dose of 4.6, 8.3 and 10.3 mg
hydrazine (free base)/kg body wt over the 2-year period], during which levels of methylation of
DNA guanine in liver, kidney and lung, and histopathologic examinations of these tissues were carried out;
dimethylnitrosamine, as a positive control, was administered
at 10 mg/l in the
drinking water (average dose of 1.1 mg/kg body wt over the 4-month measurement period). Both
7-methylguanine and
O6-methylguanine were readily detectable at 6 months exposure in hamsters given
hydrazine or
dimethylnitrosamine; in
hydrazine-treated animals only trace amounts of these bases could be detected after 12 months exposure; these bases were again detected in liver
DNA at exposure times of 18 and 24 months.
Hepatocellular carcinomas were observed in hamsters treated at the highest dose of
hydrazine sulfate after 78 weeks of exposure; the incidence of
liver cancer was dose-related over the course of the experiment: 32% for hamsters exposed to 510 mg
hydrazine sulfate/l, 12% for 340 mg/l and none at 170 mg/l. Hamsters given
dimethylnitrosamine developed high levels of
7-methylguanine and even higher levels of
O6-methylguanine and both liver
cholangiocellular carcinomas (73% incidence), as reported before, and
hepatocellular carcinomas (27% incidence), a new finding. These results demonstrate for the first time that
hydrazine is a liver
carcinogen in the hamster and provide new information regarding the accumulation of DNA damage during the entire induction period for the
carcinomas.