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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1997-10-16
pubmed:abstractText
We investigated the mutagenic activation of 2-naphthylamine (2-NA), 3,2'-dimethyl-4-aminobiphenyl (DMAB), and 3,3'-dichlorobenzidine (DCB), bladder carcinogens, by renal and bladder microsomes and by purified P450s using the umu gene expression system, which detects DNA damage. Mouse renal microsomes had high mutagenic activation toward DCB and low activity toward 2-NA. Purified mouse Cyp4b1 also had high mutagenic activity toward DCB. Anti-Cyp4b1 antibody efficiently inhibited DCB bioactivation by mouse renal microsomes with a high Cyp4b1 content. Lauric acid, a substrate of Cyp4b1, efficiently inhibited DCB bioactivation by renal and bladder microsomes of the mouse and by purified Cyp4b1. To assess the contribution of CYP4B1 to bladder carcinoma, further investigation was done with the umu test and an immunochemical study. Ten forms of purified rat P450s including rat CYP4B1 were used in the umu test for 2-NA, DMAB, and DCB. CYP4B1 had the highest activity toward DMAB and DCB. Other P450s had activities of less than 20% that of CYP4B1. CYP4B1 also activated 2-NA, but its activity was about 10% of that toward DMAB or DCB. Rat bladder epithelium was stained specifically with anti-Cyp4b1 antibody, indicating the presence of CYP4B1 in the rat bladder mucosa. Also, CYP4B1 mRNA was detected by northern blotting and reverse transcription-polymerase chain reaction (RT-PCR). These findings suggested that CYP4B1 could contribute to the initiation of carcinogenesis in rat and mouse bladder by activation of aromatic amines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
677-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9310344-Animals, pubmed-meshheading:9310344-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:9310344-Biotransformation, pubmed-meshheading:9310344-Blotting, Northern, pubmed-meshheading:9310344-Blotting, Western, pubmed-meshheading:9310344-Carcinogens, pubmed-meshheading:9310344-Cytochrome P-450 Enzyme System, pubmed-meshheading:9310344-Gene Expression, pubmed-meshheading:9310344-Kidney, pubmed-meshheading:9310344-Male, pubmed-meshheading:9310344-Mice, pubmed-meshheading:9310344-Mice, Inbred BALB C, pubmed-meshheading:9310344-Microsomes, pubmed-meshheading:9310344-Mucous Membrane, pubmed-meshheading:9310344-Mutagens, pubmed-meshheading:9310344-Rats, pubmed-meshheading:9310344-Rats, Inbred F344, pubmed-meshheading:9310344-Salmonella typhimurium, pubmed-meshheading:9310344-Urinary Bladder, pubmed-meshheading:9310344-Urinary Bladder Neoplasms
pubmed:year
1997
pubmed:articleTitle
Mutagenic activation of urinary bladder carcinogens by CYP4B1 and the presence of CYP4B1 in bladder mucosa.
pubmed:affiliation
Laboratory of Chemistry, Osaka City University Medical School, Osaka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't