Factors influencing the initiation by gamma rays of hepatocarcinogenesis in the rat.

Abstract

F344 male rats were irradiated once with 6 G of cesium 137 gamma rays at various times after a two-thirds partial hepatectomy (PH) and then fed a diet containing the liver tumor promoter phenobarbital to evoke the expression of initiated hepatocytes. Yields of hepatocellular neoplasms were enumerated at 45 weeks after irradiation. Although proliferating hepatocytes in regenerating livers appeared to have increased risk of initiation by gamma rays, there was no apparent variation in risk among groups that were treated at times when hepatocytes were in different portions of the cell cycle (G1, S, G2/M). Gamma irradiation delayed the onsets of DNA synthesis and mitosis by proliferating hepatocytes by 18-20 h. The rate of rejoining of radiation-induced DNA strand breaks was analyzed in primary cultures of hepatocytes; 98% of the strand breaks were rejoined within 30 min after irradiation. Efficient repair of certain types of radiation-induced damage to DNA before the damaged DNA is replicated should cause a substantial reduction in the probability of induction of base-substitution mutations. Hepatocellular islands and neoplasms that were initiated by gamma rays may be derived from proliferating hepatocytes which incurred other radiation-induced DNA damages such as chromosomal aberrations.