THE EFFECT OF CORTISONE ON DNA CONTENT OF RAT HEPATOCYTES

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Abstract
Male Wistar strain rats of about 120 g body weight were treated with cortisone (25 mg/day by intramuscular injection for from 1 to 5 days); X-irradiation (1300 r in air dose); and by a combination of these agents. They were killed after from 1 to 5 doses of cortisone acetate, from 1 to 5 days after X-irradiation, and from 1 to 5 days after administration of both agents. Liver of animals was excised and in one portion, the nuclei (both parenchymal and non-parenchymal) were enumerated using a hemacytometer, and in a second portion the DNA/gram of liver was determined by Schneider procedure. In the hormone-treated animals there was a fall in the average DNA/nucleus from 1 to 5 days. In the X-irradiated animal, there was a fall in the average DNA/nucleus from 1 to 3 days and then a return to normal at 5 days. In the animals subjected to both types of treatment there was a steady fall from day 1 to day 5, though at the end of 5 days the DNA/nucleus was not as low as in the animals treated by hormone alone. 3 days after discontinuation of cortisone, DNA/average nucleus was normal. p32 was administered during the second 24 hours after discontinuation of hormone and there was observed very little increase in incorporation by DNA in over that observed in animals receiving no hormone. This same type of measurement was made on the 4th day after X-irradiation and results were similar. There was no evidence that DNA was synthesized actively following discontinuation of cortisone or during recovery stage after X-irradiation and hence it seemed unlikely that DNA was destroyed by these agents. Rather, this represents repolymerization of DNA which had become depolymerized under the influence of X-irradiation or cortisone. This same explanation was used to account for the fall in average DNA/nucleus as measured by the extraction of DNA by hot acid. Through analysis of their data, the authors also suggested that a simple loss of polyploid hepatocytes would also explain the experimental observations.