The objectives of these studies were to study the effects of six, age, strain, and environmental chemicals on cytochrome P-450 enzymes and relate these changes to the ability of the liver to metabolize steroids and foreign compounds. 1. Cytochrome P-450g is highly variable in outbred CD rats (high and low populations) and absent in the Fischer rat. It is male specific and found only after puberty. This enzyme metabolizes steroids but there were no significant differences in steroid hydroxylation between high and low phenotypes of CD rats. 2. Cytochrome P-450 UT-H (debrisoquine form) and cytochrome P-450 2c (a male specific isozyme) were decreased (40% and 90%) by a toxic PCB isomer, and to a lesser extent by 3-MC and phenobarbital. Metabolism of testosterone by liver microsomes (P-4502c mediated) at the 2- and 16- positions was also decreased dramatically. Decreases in 6Beta-hydroxylation of testosterone and increases in 7Alpha-hydroxylation also occurred, and may be involved in changes in endocrine status of the PCB exposed rat. 3. The possible binding of hexachlorobenzene to the Ah receptor and its induction of P1-450 and P3-450 is being investigated. Some evidence for involvement of the Ah locus in the action of hexachlorobenzene is indicated. The goal of this project is to better understand changes in the ability of the liver to metabolize hormones and foreign chemicals after exposure to environmental chemicals.
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