Failure of x-ray irradiation to inhibit ribonucleic acid polymerase activity in regenerating rat liver nuclei

Abstract

In regenerating rat liver, inhibition of DNA synthesis following whole- body irradiation during the so-called postmitotic presynthetic period G1, is accompanied by a significant decrease of thymidylate kinase and DNA polymerase activities. RNA polyngerase activity also increases in rat liver nuclei after partial hepatectomy, and this RNA may be messenger RNA for protein-synthesizing systems. The effects of x irradiation on this RNA polymerase activity 2, 4, 6, and 12 hr after partial hepatectomy, i.e., during the G1 period, were investigated. The hepatectomized rats received 750 or 1500 r of wholebody x irradiation 2 and 12 hr later and were killed 12 or 18 hr after hepatectomy, since RNA polymerase activity starts to increase 9 hr after the operation, reaches a maximum between 12 and 18 hr, and decreases significantly after 24 hr. RNA polymerase activity in nonhepatectomized control rat liver rose from 196 mu mu moles/mg to levels 12 and 18 hr after partial hepatectomy of 452 and 442 mu mu moles/ mg, respectively. Results in irradiated rats show that the mechanism which enhances the RNA polymerase activity in regenerating livers is not radiosensitive at doses up to 1500 r, since the pattern of increase is not altered when xmore » rays are administered up to 9 hr after hepatectomy. The enzyme itself is not radiosensitive up to the same dose, since x-ray exposure 12 hr after hepatectomy, when enzymatic activity reaches a maximum, did not lead to any decrease 6 hr later (i.e., 18 hr after operation). Thus the increase in RNA polymerase activity after hepatectomy is unaffected by x irradiation. These data suggest several hypotheses, which are discussed, to explain how irradiation, through alteration of nuclear RNA metabolism, affects the information of enzymes required for DNA synthesis in regenerating rat liver such as thymidylate kinase and DNA polyngerase. Although RNA polymerase activity is unaffected by irradiation, the previously reported disturbance of the metabolism of nuclear RNA after x-ray exposure could be explained by a decrease in nuclear phosphorylations. There is probably a disturbance in the biosynthesis of the nucleolar RNA, which plays a part in protein synthesis. Moreover, in the case of high doses of x rays (1500 r), DNA may be damaged, resulting in the formation of nonsense RNA, since RNA polymerase can use nonspecific DNA as template. The disturbance in protein synthesis induced by x smic metabolism; thus a decrease of mitochondrial oxidative phosphorylations, such as described in the liver after irradiation, can also account for inhibition of synthesis of enzymes required for the biosynthesis of DNA, without implying any disturbance in the metabolism of nuclear RNA's. It is suggested that several of these mechanisms are involved. (BBB)« less