COMPARISON OF DRUG-METABOLIZING ENZYMES IN LIVER AND KIDNEYS FROM HOMOZYGOUS NUDE SWISS, HETEROZYGOUS NORMAL SWISS, HOMOZYGOUS NORMAL SWISS AND DBA/2 MICE

Abstract

The hepatic and renal microsomal drug metabolizing enzyme systems were isolated from homozygous nude Swiss (nu/nu), heterozygous normal Swiss (nu/+), homozygous normal Swiss(+/+) and DBA/2 mice. Microsomal protein and cytochrome P-450 concentrations were measured and the activity of ethylmorphine demethylase, aniline hydroxylase, aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase were determined. Hepatic microsomes from both experimental groups carrying the nude gene were able to metabolize aniline and ethylmorphine more rapidly (20% and 36%, respectively) than the DBA/2 or Swiss homozygous normal mice. No difference between test groups was observed for hepatic aryl hydrocarbon hydroxylase or UDP-glucuronyl transferase activity. Kidney microsomes from mice carrying the nude gene had approximately twice the aryl hydrocarbon hydroxylase activity of the other 2 experimental groups. Renal mixed-function oxidase pathways measured for the homozygous nude mouse showed a higher overall rate of activity than the other 3 experimental groups. No significant difference in renal UDP-glucuronyl transferase was observed between mouse groups.