Effect of hypophysectomy on persistence of methylated purines in rat liver deoxyribonucleic acid after administration of dimethylnitrosamine

The formation of methylated purines in DNA following dimethylnitrosamine administration was studied in control and hypophysectomized rats. When given the same dose of this carcinogen (in mg/kg body weight) the formation of the major product 7-methylguanine and of the minor products 1-, 3- and 7-methyladenine and 3-methylguanine was slightly greater in the livers of hypophysectomized rats than in controls. The rate of loss of these products from the DNA was not affected by hypophysectomy. O⁶-Methylguanine levels were significantly greater in the hepatic DNA of hypophysectomized rats compared to controls after doses of dimethylnitrosamine ranging from 1 to 20 mg/kg. This difference was due to a slower rate of loss of this purine from the DNA in the hypothysectomized rats. Growth hormone treatment increased the rate of removal of O⁶-methylguanine in the hypophysectomized rats but did not restore the activity to that found in controls. The possible significance of these results in the induction of tumors by dimethylnitrosamine is discussed.