The influence of ddt and γ-chlordane on the metabolism of hexobarbital and zoxazoalamine in two mouse strains

Some studies and comments on hepatic and extrahepatic microsomal toxication-detoxication systems. A limited discussion of some of the heterogeneities of these systems and of their responses to stimulation of enzyme "induction".

“…A very similar picture emerged with DDT. DDT did not affect most mouse liver microsomal systems enough for the changes to be measured, whereas the related inducer, chlordane, could cause quantifiable responses in mice (35,36). Again the accumulating evidence suggested a quantitative, not qualitative, difference in mouse vs. rat response to the hepatic enzyme inducers, DDT and benzpyrene.…”

“…In later work, we discovered an apparent difference in response of rats vs. mice to induction of hepatic toxication-detoxication systems by benzpyrene and DDT (35)(36)(37)(38)(39)(40)(41). Thus, at doses and schedules of dosing and at times after last dose of the inducer that clearly established hepatic microsomal enzyme induction by DDT or benzpyrene in rats and other species including monkeys (42), the mouse did not show such induction or showed it only marginally (36). A detailed study of the mouse liver systems failed to uncover any evidence for enzyme induction by benzpyrene (38,39), although we were able to show some enzyme induction by the related, but more potent polycyclic hydrocarbon 3-methylcholanthrene. Others have reported that mice are less likely to respond to hepatic microsomal enzyme inducers of the polycyclic hydrocarbon class than are other species, especially rats (43).…”

Some Studies and Comments on Hepatic and Extrahepatic Microsomal Toxication-Detoxication Systems: A Limited Discussion of Some of the Heterogeneities of These Systems and of Their Responses to Stimulation of Enzyme "Induction"

“…In later work, we discovered an apparent difference in response of rats vs. mice to induction of hepatic toxication-detoxication systems by benzpyrene and DDT (35)(36)(37)(38)(39)(40)(41). Thus, at doses and schedules of dosing and at times after last dose of the inducer that clearly established hepatic microsomal enzyme induction by DDT or benzpyrene in rats and other species including monkeys (42), the mouse did not show such induction or showed it only marginally (36).…”

“…Thus, at doses and schedules of dosing and at times after last dose of the inducer that clearly established hepatic microsomal enzyme induction by DDT or benzpyrene in rats and other species including monkeys (42), the mouse did not show such induction or showed it only marginally (36). A detailed study of the mouse liver systems failed to uncover any evidence for enzyme induction by benzpyrene (38,39), although we were able to show some enzyme induction by the related, but more potent polycyclic hydrocarbon 3-methylcholanthrene.…”

“…DDT did not affect most mouse liver microsomal systems enough for the changes to be measured, whereas the related inducer, chlordane, could cause quantifiable responses in mice (35,36 Our most recent work with mouse liver responses to benzpyrene and DDT has used the same strain of mouse that we started with at Iowa, i.e., mice which did not respond to benzpyrene, but did respond to 3-methylcholanthrene and very slightly to DDT. In these latest studies we have greatly increased the dose of inducer used and shortened the period between last dose of inducer and the time of enzyme assay.…”