Altered expression of immunohistochemically detected cytochrome P-450 component(s) in nitrosamine-induced rat urinary bladder lesion.
Male ACI/N rats were treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water, and in conjunction with histological examination, the changes of the expressed cytochrome P-450 components in the urothelium and other tissues (liver, kidney, esophagus, intestines) were examined by means of immunohistochemistry. Frozen tissue sections were prepared and immunostained with anti-rat cytochrome P-450 monoclonal antibodies and an avidin-biotin-peroxidase complex. Monoclonal antibodies used were APH-3 and APH-8 raised against a high-spin form of cytochrome P-448, APL-1 and APL-2 against a low-spin form of cytochrome P-448, and APF-3 against cytochrome P-450. BBN-induced qualitative and quantitative changes of cytochrome P-450 components recognized by these monoclonal antibodies were not observed in tissues other than the bladder. Untreated rat bladder epithelium was not stained with any of these 5 monoclonal antibodies. The treatment with BBN for more than 3 weeks, however, resulted in the expression of cytochrome P-450 component(s) recognized by APH-8 antibody. This cytochrome P-450 component increased with the advance of carcinogenic changes in the urothelium. The component reactive with AHP-8 was also detected in the cancer tissues of transplantation lines of rat bladder cancers. In contrast, the cytochrome P-450 components recognized by APL-1, APL-2 or APF-3 were undetectable or present at low levels throughout the BBN carcinogenesis. These results suggest that a certain cytochrome P-450 component(s), probably a high-spin form of cytochrome P-448, is selectively induced in urothelium in association with neoplastic bladder lesion.
D000818:Animals; D002085:Butylhydroxybutylnitrosamine; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D001743:Urinary Bladder / Q000201:enzymology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000201:enzymology*
D002085:Butylhydroxybutylnitrosamine; D003577:Cytochrome P-450 Enzyme System