Hydroxyurea-sensitive thymidine incorporation in rat liver and kidney following administration of dimethylnitrosamine

Abstract

In rats treated with dimethylnitrosamine (DMN), the sensitivity of [3H] thymidine incorporation to inhibition by hydroxyurea was determined in the liver and kidney. A 70% inhibition was produced in control animals with doses of hydroxyurea from 50 to 250 mg/kg body wt. Twelve hours after administration of DMN, hepatic thymidine incorporation was unaffected by 50 mg/kg hydroxyurea, progressive reduction in incorporation occurred as the dose of inhibitor was increased. A similar result was obtained in kidney only by dietary conditioning of rats to ensure a high renal metabolism of the DMN. In contrast, at 72 h after DMN treatment thymidine incorporation in both liver and kidney was rapidly inhibited by administration of 50 mg/kg hydroxyurea. The data, assessed together with various parameters of DMN-induced repair and replicative DNA synthesis, suggest the use of hydroxyurea as a means to study DNA repair in intact animals.