Renal and hepatic nucleic acid metabolism in neonates: relation to experimental duration, chlorphentermine dose as well as subsequent withdrawal.

Daily oral administration of either 20, 40 or 60 mg/kg chlorphentermine for 7 days significantly increased liver and kidney DNA levels, which were not elevated further even after a 3 week treatment period. Although cessation of drug administration for 3 weeks resulted in a return of hepatic DNA levels to control values, a rise in renal DNA was still observed after this withdrawal period. Whereas 20 mg/kg chlorphentermine for 7 days failed to markedly alter the incorporation of thymidine into kidney and liver DNA, significant enhancement was noted in neonates receiving 40 or 60 mg/kg drug and quantitatively greater incorporation occurred when the agent was given for 21 days. While a signficant augmentation in nucleic acids synthesis was seen 1 week after animals were removed from 40 or 60 mg/kg anorectic, a restoration to control levels occurred after a 3 week abstinence period. Treatment with 20 mg/kg for 1 week followed by withdrawal resulted in a significant rise in the incorporation of thymidine into renal and hepatic DNA. In contrast, drug administration for 3 weeks followed by 21 days abstinence resulted in a return to control levels in the incorporation of thymidine into kidney and liver DNA, except for renal tissue removed from 20 mg/kg. Our data demonstrate that the chlorphentermine-induced alterations in renal and hepatic DNA metabolism are dose-dependent, related to duration of exposure as well as reversible.