Effects of Age and Obesity on the Metabolism of Lindane by Black a/a, Yellow (A sup vy)/a, and Pseudoagouti (A sup vy)/a Phenotypes of (YS x VY) F1 Hybrid Mice

摘要

Lindane (hexachlorocyclohexane) has been shown to produce hepatomas in some strains of mice but not in others. Genetic factors and/or altered metabolism may plan a role in the susceptibility to lindane-induced hepatomas. Previous investigations have demonstrated that the viable yellow Avy mutation increases susceptibility to the formation of hepatomas in the mouse. The study reports the effect of age and obesity on the comparative metabolism and disposition of lindane in obese yellow Avy/a and in lean pseudoagouti Avy/a and black a/a phenotypes of (YS x VY) F-1 hybrid female mice at 8, 17, 30, 56, and 86 weeks of age. Twenty-four hours prior to sacrifice the mice were dosed p.o. with 18 mg lindane (containing 55 micro Ci (U-14C) lindane)/kg. Aging altered the biotransformation of lindane such that while the excretion of lindane and its metabolites declined, the proportion of conjugated and polar metabolites were elevated. Tissue storage was elevated in older animals.