The biosynthesis of pyrimidine nucleotides and cytochrome P-450 content in rat liver microsomes after the administration of α-hexachlorocyclohexane (in vivo study)

Summary The administration of α-hexachlorocyclohexane (α-HCH) increases the utilization of [2- 14 C] orotic acid for the synthesis of uridine components of the liver and decreases the utilization for the synthesis of cytidine components. These changes are affected to a different degree depending on the dose administered. The specific activities of uridine components increase from 25 to 200 mg α-HCH/kg body wt., the depression of specific activities of cytidine nucleotides is maximal after the administration of 25 mg of α-HCH/kg. Changes in the utilization of [2- 14 C] orotic acid measured in terms of the ratio of specific activity of cytosine to uracil are inversely proportional to changes in cytochrome P -450 level. The increase of the cytochrome P -450 is highest after the administration of low dose of the drug; doses of 100 mg/kg and higher do not increase the cytochrome P -450 level any further. The increase of the specific activities of the uridine components and the decrease of specific activities of cytidine components can be observed even 11 days after the administration of a single dose of α-HCH. The utilization of [U- 14 C palmitic acid for the synthesis of microsomal phospholipids increases 75 min after the administration of α-HCH; the specific activity of microsomal neutral lipids simultaneously decreases.