Inhibition of the Development of Hepatic Microsomal Detoxification Enzymes by X-Irradiation

摘要

Studies were conducted on the influence of X-ray and some radiomimetic drugs on the development of several hepatic microsomal enzymes in the livers of young, male rats, on the activity of these enzymes in the livers of adult animals, and on induced enzyme synthesis by phenobarbital. Exposure of 23-day old male rats to doses from 100 r to 400 r of X-ray inhibited development of phosphorothioate detoxification, the hexobarbital oxidizing enzyme, and N-demethylase. O-demethylase activity, which reaches the adult level by 23 days of age, was not affected by X-ray. Radiomimetic drugs, including mechlorethanine hydrochloride (HN2) and cyclophosphamide (Cytoxan), inhibited development of the enzymes in weanling, male rats and they also inhibited the activity of the enzymes in the livers of adults. Neither radiation nor radiomimetic drugs inhibited the rapid induction of enzyme activity caused by phenobarbital administration. The results of these studies indicate that radiation specifically inhibits the synthesis of increased microsomal enzyme activity in the livers of young male rats. Since irradiation of only the head caused the inhibition of enzyme development, it appears that radiation interferes with some process involving hormonal regulation of microsome enzyme synthesis. Radiomimetic drugs have the additional ability to inhibit the enzyme activity in adult animals possibly through inhibition of synthesis required for maintenance of normal enzyme levels. (Author)