Modification of folic acid-induced changes in renal nucleic acid and protein synthesis by actinomycin D and cycloheximide.

Abstract

Parenteral administration of folic acid to rats produces marked increases in the rates of synthesis of protein, RNA and DNA in the kidney. Basic nuclear protein synthesis is increased within 1 hour of folate administration with a sharper increase appearing about 18 hours and reaching a maximum about 26 hours. RNA synthesis increases to reach a maximum at 12 hours after folate before declining to normal levels at 24 hours. The increase in the rate of DNA synthesis commences at about 18 hours and reaches a maximum, about 20 times above control levels, about 32 hours after folate.Using the increased rate of DNA synthesis normally seen 26 hours after folate as a reference point, actinomycin D was found to produce a very marked depression of DNA synthesis when administered between 0 and 4 hours after folate; at longer time intervals this depression became less marked and when actinomycin D was given at 20 hours no effect was observed. Actinomycin D, given at the same time as folic acid, also abolished the increase in the rate of RNA synthesis normally seen 12 hours after folate.In contrast to the time dependent effect of actinomycin D, cycloheximide produced a similarly profound decrease in the rate of DNA synthesis, measured 26 hours after folate, when the drug was given at any time between 0 and 25 hours after folate.These results suggest that the complete requirement for increased RNA synthesis has been met by the time that increased DNA synthesis begins at 18 hours after folate administration, but that there is continuous need for newly synthesised protein both before and during the period of increased DNA synthesis.