THE EFFECT OF CORTISONE ON DNA CONTENT OF RAT HEPATOCYTES

Rats were treated with cortisone, x-radiation, and both agents in combination, and the effect noted on the DNA content of hepatocytes. Nuclei were enumerated both in whole liver homogenates and following isolation. The incorporation of P³² into DNA was also studied in relation to these agents. The following observations were made:— 1.The DNA content of nuclei fell both during cortisone administration and following x-radiation. In the former instance, the fall was progressive with continuing administration of hormone; in the latter instance, there was a return to normal 5 days after radiation. 2. Cortisone administration to x-radiated rats caused a fall in DNA/nucleus and prevented the return to normal at 5 days. 3. There was no evidence that the effects of cortisone and x-rays were additive in reducing DNA/nucleus. 4. These data indicate an alteration in DNA/nucleus, but simple changes in ploidy cannot be excluded. Either explanation requires that the agents used affect the DNA of non-regenerating nuclei. 5. Cortisone interfered with the incorporation of P³² into the DNA of regenerating liver. Only a small effect on DNA synthesis in resting liver was observed with cortisone or x-radiation. 6. DNA content of nuclei returned to normal 5 days after x-radiation and 3 days after discontinuance of cortisone. Slight increase in the incorporation of P³² by DNA was observed during recovery phases. 7. The hypothesis is proposed that the apparent losses and increases in DNA/nucleus were due to depolymerization and repolymerization of DNA. Following x-radiation and/or cortisone administration, it is proposed that some DNA is depolymerized and becomes cold acid-soluble and dissociated from organized chromatin. Later, conditions are such that this degraded DNA is repolymerized. 8. These data might be interpreted to indicate that a portion of the DNA is not essential to cell integrity; alternatively, there may be two or more species of DNA, one of which is more readily affected by the agents investigated in the present report.