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There are several publications discussing the mechanism of action of hydrazine in rat and mouse suggesting that treatment with hydrazine disturb the balance of methylation and demethylation on N-7  and O-6 of guanine resulting in liver toxicity. Therefore, It is plausible that liver tumours after long-term high dose exposure to hydrazine  are secondary to liver toxicity.

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There are several publications discussing the mechanism of action of hydrazine in rat and mouse suggesting a dose-dependent increase in liver DNA methylation after single and repeated oral administration. In this context it is discussed that treatment with hydrazine disturb the balance of methylation and demethylation on N-7 and O-6 of guanine by inhibiting the demethylation which would result in accumulation of the methylated purines in the liver DNA (see also DFG 1989). Dose-response studies in rats revealed a single oral dose of 0.1 mg/kg as a starting dose for effects on liver DNA methylation (borderline effect, clear effects with 10 mg/kg; van Delft 1997; clear effect at 30 mg/kg; Becker et al. 1981). After the third of four oral doses of 3 mg/kg increase of 7-methylguanine was observed as trace and readily detectable after 4 treatments (Becker et al. 1981). Evidence of liver toxicity was shown at 2.5 mg/kg (exposure for 1-10 days; decrease of GSH, increase of triglycerides; Jenner & Timbrell 1992) and 3 mg/kg (3-4 doses; Becker et al. 1981). Therefore it is plausible that the liver tumours after long-term high dose exposure are secondary to liver toxicity and alteration of the balance of methylation and demethylation