Changes in aldehyde dehydrogenase during rat urinary bladder carcinogenesis.
We have reported that normal rat urinary bladder possesses significant amounts of an aldehyde dehydrogenase (class 3 ALDH) expressed during hepatocarcinogenesis, but not detectable in normal liver. Changes in expression of both liver and bladder ALDH during N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis were studied. The ALDH phenotype was determined at intervals over 42 weeks by histochemical analysis, total ALDH activity assays and gel electrophoresis using propionaldehyde and NAD (P-NAD) which characterizes class 1 and 2 ALDH, or benzaldehyde and NADP (B-NADP) to determine class 3 ALDH. By total activity assays and gel electrophoresis, there was a significant decrease in bladder class 3 ALDH activity during weeks 5-15. Histochemical analysis clearly demonstrates changes in ALDH early in neoplastic development. Intense staining with B-NADP in regions of hyperplasia was first detectable at week 10. Staining in hyperplastic regions was accompanied by a significant decrease in ADLH in neighboring, apparently normal urothelium. As the urothelium became more abnormal, class 3 ALDH activity increased. By week 25, the bladder class 3 ALDH activity of BBN-treated animals was 2 times greater than the control group class 3 ALDH activity. Histochemically, all papillomas and carcinomas examined possessed class 3 ALDH. However, staining was heterogeneous within the lesions. Bladder neoplasm class 3 ALDH specific activity was greater than control group class 3 ALDH activity in 70% of papillomas and carcinomas. These results suggest events may be occurring in bladder similar to those in liver which alter expression of aldehyde dehydrogenase during carcinogenesis.
Campbell
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P
Department of Biology, University of Alabama, Tuscaloosa 35487.
Irving
C C
CC
Lindahl
R
R
D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002085:Butylhydroxybutylnitrosamine; D002277:Carcinoma / Q000201:enzymology*; D006651:Histocytochemistry; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D010212:Papilloma / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D001743:Urinary Bladder / Q000201:enzymology; D001749:Urinary Bladder Neoplasms / Q000201:enzymology*
D007527:Isoenzymes; D002085:Butylhydroxybutylnitrosamine; D000444:Aldehyde Dehydrogenase