Absence of p53 gene mutations in rat colon carcinomas induced through the synergistic interaction between methylazoxymethanol and X-irradiation.
p53 is one the most frequently mutated genes found in human colonic tumors. Because colonic neoplasms induced in rats by certain chemical carcinogens are similar to human colonic tumors in their histological features and proliferation characteristics, the rat has been used as an experimental model to study the pathogenesis of colon cancer. However, p53 mutations were not detected in the chemically induced colonic tumors analyzed for p53 mutations. X-irradiation has also been shown to induce colonic neoplasms in rats that resemble human colonic tumors histopathologically. Because the incidence of colonic tumors induced by methylazoxymethanol (MAM) in rats was shown to be enhanced by X-irradiation, we immunohistochemically analyzed these colonic carcinomas for the presence of p53 gene mutations. The immunohistochemical analyses clearly showed the absence of nuclear immunoreactivity in all ten tumors examined. The results from the present study indicate that point mutations in p53, at least in the coding region, are not involved in the development of colon cancer induced by the combination of MAM and X-irradiation. Our observations, together with the data from previous studies, further suggest that rat colon carcinogenesis, unlike human colon cancer, may not involve p53 mutation as an obligatory event.
Shivapurkar
N
N
Institute for Disease Prevention, George Washington University Medical Center, Washington, D.C. 20037, USA.
Nikula
K J
KJ
Tanaka
T
T
Tang
Z C
ZC
Alabaster
O
O
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics; D000818:Animals; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000737:chemistry / Q000209:etiology / Q000235:genetics*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives*; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D017354:Point Mutation; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014916:Whole-Body Irradiation
D002273:Carcinogens; D016159:Tumor Suppressor Protein p53; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol