Liver growth and mixed-function oxidase activity: Dose-dependent stimulatory and inhibitory effects of α-hexachlorocyclohexane

Summary -hexachlorocyclohexane (-HCH) elicits liver growth and stimulation of hepatic microsomal mixed-function oxidase. In the present study the extent of these changes was determined in rats 2, 4 and 6 days after treatment with doses of -HCH ranging from 1 to 600 mg/kg. Above the respective threshold doses liver mass, liver DNA, and the rate of aminopyrine demethylation increased in proportion to the log dose. Threshold doses were calculated to be 30 mg/kg for the increase of liver weight and DNA, and 5 mg/kg for the stimulation of aminopyrine demethylation.Liver mass and liver DNA continued to increase up to the highest dose used; in contrast, the rate of aminopyrine demethylation declined at doses exceeding 200 mg/kg. This decline seems to be due to inhibition by -HCH retained in the microsomal fraction: -HCH is a potent, apparently competitive inhibitor of aminopyrine demethylation, and gaschromatographic determinations revealed that the amount of -HCH retained in the microsomes is sufficient to produce considerable inhibition of the enzymatic reaction.Abbreviations -HCH -1,2,3,4,5,6-hexachlorocyclohexane, -benzene hexachloride - EL 241 ,-bis(p-chlorophenyl)-3-pyridinemethanol] - RLW relative liver weight = liver weight in percent of body weight