Possible involvement of O6-methylguanine formation and p53 dysfunction in mouse urinary bladder carcinogenesis.
The significance of O6-methylguanine formation in urinary bladder carcinogenesis was examined using O6-methylguanine-DNA methyltransferase (MGMT) transgenic mice carrying the ada gene. The ada MGMT transgenic mice demonstrated no differences in development of carcinogens-induced urinary bladder carcinomas compared with non-transgenic mice. Furthermore, no variation in p53 mutation frequency was evident between the two groups. The results indicated that other repair systems may have an important role for urinary bladder carcinogenesis. p53 knockout mice showed high sensitivity to urinary bladder carcinogens and increased cell proliferation plays an important role in urinary bladder carcinogenicity of p53 knockout mice. In addition, p53 knockout mice have an organ-specific increased sensitivity to carcinogenicity.
Fukushima
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Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, 545-8585, Osaka, Japan. fukuchan@med.osaka-cu.ac.jp
D000818:Animals; D002085:Butylhydroxybutylnitrosamine; D002101:Cacodylic Acid / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004252:DNA Mutational Analysis; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism*; D006801:Humans; D008297:Male; D008770:Methylnitrosourea; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism
D002273:Carcinogens; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D002085:Butylhydroxybutylnitrosamine; D006147:Guanine; D008770:Methylnitrosourea; C008449:O-(6)-methylguanine; D002101:Cacodylic Acid; D019853:O(6)-Methylguanine-DNA Methyltransferase