Circadian fluctuations in the activity of DNA-dependent RNA polymerases I and II in the nuclei isolated from mouse tissues and the significance for pharmacological and toxicological studies on transcription.

Abstract

For pharmacological and toxicological studies on the effect of drugs on transcriptional processes the basic fluctuation in activity during a 24-h period must be known. We have measured the activity of nuclear and mitochondrial DNA-dependent RNA polymerases in cell fractions from mice kept under defined dark/light and feeding schedules. The following results have been obtained: 1. Circadian variations in the activity of RNA polymerases are especially pronounced in the nuclei of liver tissue. These changes depend predominantly on feeding habits and they are comparatively independent on the dark/light schedule. A maximum in the activity of nuclear DNA dependent RNA polymerases can be observed shortely after the beginning of the feeding period. 2. The nuclei isolated from other tissues, such as brain, kidney or embryos during the late stage of embryogenesis shown considerably smaller, if any, fluctuations in connection with the feeding habits. These tissues seem to be especially suitable for pharmacological or toxicological studies on transcriptional processes. 3. While both nuclear DNA-dependent RNA polymerases shown a strong dependence on the feeding habits no obvious circadian viriations can be observed in the activity of the DNA-dependent RNA polymerase localized in the mitochondrial fractions of the same tissue. The regulation of these polymerases in different cell compartments apparently occurs quite independently. The conclusions for the design of experiments on induction processes occurring in liver tissues, drawn from the results presented, are discussed.