Androgen regulation of CYP4B1 responsible for mutagenic activation of bladder carcinogens in the rat bladder: detection of CYP4B1 mRNA by competitive reverse transcription-polymerase chain reaction.
Significant sex differences exist among cases of bladder cancer in humans as well as in experimental animals such as rats. Aromatic amines such as benzidine and 2-naphthylamine are known to induce bladder cancer. These carcinogenic amines are activated to genotoxic substances by cytochrome P 450 CYP4B1, which is present in bladder mucosa. In this study, regulation of CYP4B1 was investigated to elucidate sex difference in bladder carcinogenesis. Competitive reverse transcription-polymerase chain reaction was used to investigate the expression of rat CYP4B1 mRNA occurring in small amounts of tissue such as bladder tissue. Expression of CYP4B1 in the bladder of male rats increased with development but not in that of female rats. Moreover, mature male rats exhibited higher expression of CYP4B1 in the bladder than did mature female rats. Castration of male rats decreased CYP4B1 levels and treatment with testosterone led to a partial recovery of CYP4B1 levels. These results indicate that CYP4B1 levels in the rat bladder are partly regulated by androgens. Furthermore, the present findings suggest that the sex difference observed in bladder carcinogenesis was due to sex-different expression of CYP4B1 in bladder tissue.
Imaoka
S
S
Department of Chemical Biology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, 545-8585, Osaka, Japan. imaoka@med.osaka-cu.ac.jp
Yoneda
Y
Y
Sugimoto
T
T
Ikemoto
S
S
Hiroi
T
T
Yamamoto
K
K
Nakatani
T
T
Funae
Y
Y
D000367:Age Factors; D000728:Androgens / Q000502:physiology*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002273:Carcinogens / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D009092:Mucous Membrane / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D001743:Urinary Bladder / Q000201:enzymology / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000209:etiology
D000728:Androgens; D002273:Carcinogens; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C095029:cytochrome P-450 CYP4B1