Inhibition of apoptosis in colon tumors induced in the rat by 2-amino-3-methylimidazo[4,5-f]quinoline.
The cooked meat mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) produces tumors at multiple sites in the F344 rat, including adenocarcinomas of the colon. In the present study, the development of IQ-induced colorectal tumors was shown to be accompanied by the progressive inhibition of programmed cell death. This was associated with increased expression of the antiapoptosis protein Bcl-2 and decreased expression of bax, a known activator of apoptosis. Carcinomas bearing high levels of bcl-2 expression exhibited low levels of p53, the tumor suppressor protein that in some circumstances has been shown to down-regulate bcl-2. Because they lack mutations in the genes commonly associated with increased cell proliferation (APC, Ki-ras, and p53) and show no evidence of microsatellite instability, IQ-induced colon tumors might arise via the deregulation of bcl-2 expression, leading to inhibition of programmed cell death.
Hayashi
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R
Department of Environmental Biochemistry, University of Hawaii, Honolulu 96822, USA.
Luk
H
H
Horio
D
D
Dashwood
R
R
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D007124:Immunoenzyme Techniques; D008297:Male; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011804:Quinolines; D051381:Rats; D011916:Rats, Inbred F344; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D002273:Carcinogens; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011804:Quinolines; D016159:Tumor Suppressor Protein p53; C029216:2-amino-3-methylimidazo(4,5-f)quinoline