Effect of Aminoacetonitrile on the Metabolism of Dimethylnitrosamine and Methylation of RNA During Liver Carcinogenesis2

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Abstract
We studied the effect of chronic aminoacetonitrile (AAN) administration on the metabolism of dimethylnitrosamine (DMNA) and on the methylation of liver RNA in rats continuously fed unlabeled carcinogen. No inhibition in the output of 14CO2 was found in rats fed DMNA after asubsequently administered dose of 14C-DMNA. The chronic administration of AAN and DMNA inhibited the production of 14CO2 by liver slices in vitro and the exhalation of 14CO2 in vivo. Three hours after a single dose of 14C-DMNA, AAN strongly inhibited the incorporation of radioactivity into liver RNA in rats that continuously received DMNA and AAN. Twenty hours after application of labeled carcinogen, AAN did not decrease the level of N-7-methylation of guanine in liver RNA. In other experiments, all 24 rats fed DMNA for 5 months developed malignant liver tu mors; 11 of 20 rats treated with DMNA and AAN had liver tumors. The results extended our previous findings by showing that the lower rate of metabolic removal of methyl groups from the carcinogen and possibly the decreased methylation rate of liver nucleic acids may be important for the selective methylation of different cell types in the rat liver during carcinogenesis.

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