Diurnal Patterns of DNA Synthesis in the Rat: Modification by Diet and Feeding Schedule

Abstract

The diurnal pattern of DNA synthesis in young rats (28 to 35 days) was investigated under various feeding regimens of a normal and a protein-deficient diet. All animals were exposed to a 12-hour light-12-hour dark cycle. With ad libitum feeding of a stock diet, the incorporation of thymidine-³H into nuclear DNA in liver varied over a fivefold range with a peak at the end of the dark period, whereas incorporation into mitochondrial DNA scarcely varied. A diet deficient in protein (3.5% protein) not only decreased the incorporation of thymidine-³H into liver DNA but also obscured the diurnal peaks observed in animals fed a diet containing 26% protein. The activity of thymidine kinase was also depressed, but the diurnal peak was still discernible though slightly delayed. The effect of feeding schedule was then studied by restricting the feeding period of a stock diet to either the first 8 hours of the dark period (close to normal feeding behavior) or to the first 8 hours of light. The 12-hour difference in the feeding period resulted in a closely corresponding difference in the timing of the peak incorporation of thymidine-³H into DNA. In rats gradually adapted to a 4-hour feeding schedule over a period of 10 days, there was a briefer but prominent peak of incorporation about 12 hours after the onset of feeding. A smaller peak was concurrently present in the adrenals but in skeletal muscle, intestinal mucosa and bone marrow there was no clear pattern of deviation from the 24-hour mean values. The results indicate that 1) in contrast to nuclear DNA, there is no prominent diurnal peak of mitochondrial DNA synthesis in liver; 2) the peak of nuclear DNA synthesis in liver is obscured by a protein-deficient diet; 3) the peak follows feeding of a normal diet by about 12 hours, independently of the light-dark cycle; and 4) with the exception of the adrenals, other tissues studied did not reveal a food-dependent peak of DNA synthesis.