Hydrazine, H2N-NH2, is widely used in industry and the military; it is acutely toxic to the liver, kidney, and central nervous system. Chronic inhalation of
hydrazine produced
squamous cell carcinomas of the nasal turbinates in Fischer 344 rats but only at exposures which led to severe
rhinitis with focal
hyperplasia and squamous
metaplasia early in the experiment; Syrian golden hamsters and C57B16 mice did not develop
cancers under the same conditions. Biancifiori and Severi (1966) showed that
oral administration of
hydrazine at growth-depressing doses induced
hepatocellular carcinomas and lung
adenomas in male rats, pulmonary
adenomas in BALB/c/Cb/Se and BALB/c/An/Se mice and pulmonary
adenocarcinomas and
hepatomas in CBA/Cb/Se mice. Swiss Webster (Crl:CFW(SW)BR) and B6C3F1(:CrlBR) male mice from Charles River Breeding Lab. in Massachusetts, USA, were fasted overnight and given 0, 5, 10, 20, or 40 mg
hydrazine per kg
body weight by
intraperitoneal injection and decapitated 24 hr later. Liver
DNA was isolated and analyzed by high performance liquid chromatography and fluorescence spectrophotometry for chemical adducts involving the
purine bases. A dose related formation of
7-methylguanine and
O6-methylguanine was observed in
DNA, with little difference between the two strains of mice. Evidence suggests that the
hydrazine reacts with endogenous
formaldehyde to form a stable intermediate, possibility
tetraformyltrisazine, which is metabolized by alcohol and
aldehyde dehydrogenases to an active methylating agent. In an experiment similar to the dose-response study, 20 mg
hydrazine/kg body wt was given to the two strains of mice, and animals were killed at 24 hr intervals to determine the persistence of these aberrant
purines in
DNA. The rates of formation of
7-methylguanine and
O6-methylguanine and the rates of disappearance of
7-methylguanine from
DNA were the same in both strains. The rate of disapperance of the promutagenic base,
O6-methylguanine, however, was an order of magnitude slower in the B6C3F1 mouse compared with the Swiss Webster mouse; the half-life of
O6-methylguanine in the B6C3F1 mouse liver
DNA was greater than 200 hr, while in Swiss Webster mouse liver
DNA, it was 17 hr. These results are compared with a similar study in the Syrian golden hamster in which the levels of
O6-methylguanine in liver
DNA were measured over a 2-yr exposure to
hydrazine; the results suggest that the B6C3F1 mouse would be highly susceptible to the hepatocarcinogenicity of
hydrazine. This susceptibility is compared with that of other species.