Immunohistochemically demonstrated altered expression of cytochrome P-450 molecular forms and epoxide hydrolase in N-ethyl-N-hydroxyethylnitrosamine-induced rat kidney and liver lesions.

A comparison of N-ethyl-N-hydroxyethylnistrosamine (EHEN)-induced preneoplastic and neoplastic lesions in the rat liver and kidney was made with respect to the expression of different drug metabolizing enzymes. Four cytochrome P-450 species (cyt. P-450 UT50, PB3a, MC1 and MC2) and microsomal epoxide hydrolase (mEHb) were investigated along with two glutathione S-transferase species (GST-P and A forms) earlier shown to be elevated in putative preneoplastic lesions in the liver and kidney, respectively. In contrast to the liver lesions, which showed clear decrease in all forms of cyt. P-450s and increase of mEHb, elevated levels of cyt. P-450 PB3a and, to a lesser extent, the other P-450 forms and early elevation to late decrease in mEHb characterized the renal tubular lesions. Thus opposite shift in enzyme phenotype was observed in carcinogen-induced focal lesions of the two organs. Variation in binding levels in the different nephron segments and zones of the liver acinus indicated physiological specialization with regard to the enzymes investigated and suggested that the altered phenotype of preneoplastic populations might be of adaptive significance.