MOUSE RENAL CYTOCHROME-P450IIE1 - IMMUNOCYTOCHEMICAL LOCALIZATION, SEX-RELATED DIFFERENCE AND REGULATION BY TESTOSTERONE

Cytochrome P450IIE1 is responsible for the metabolic activation of N-nitrosodimethylamine and a variety of other chemicals. Renal P450IIE1 was shown previously to be regulated by testosterone in C3H/HeJ and BALB/c mice. The present study investigated the distribution of cytochrome P450IIE1 in the kidneys of C3H/HeJ and BALB/c mice. The amount of P450IIE1 was immunotitrated by immunohistochemistry using polyclonal antibodies against rat P450IIE1. Strong immunoreactivity was identified mainly in the cortical tubules, including proximal tubules and some distal tubules. Weak immunoreactivity was also observed in the outer medulla when higher concentrations of antibodies were used. Much higher immunostaining was observed in male mice than in female mice when identical antibody dilutions were used. The renal P450IIE1 level in females was elevated to the same level as that in males 24 hr after administration of testosterone. The results showed a specific cellular localization of cytochrome P450IIE1 in mouse kidney. The findings may lead to a better understanding of the site-specific renal toxicity and carcinogenesis due to the activation of chemicals by cytochrome P450IIE1.