No involvement of APC gene mutations in ulcerative colitis-associated rat colon carcinogenesis induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate.
A rat model for human ulcerative colitis (UC) has been developed by using 1-hydroxyanthraquinone (1-HA) to cause severe inflammation of colonic mucosa. 1-HA also has synergistic effects on the carcinogenicity of methylazoxymethanol (MAM) acetate in the rat colon. In this study, four adenomas and 16 adenocarcinomas induced in male F344 rats by 1-HA and MAM acetate were examined for mutations in the entire coding regions and introns flanking coding exons of the APC gene by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and PCR-restriction-SSCP analyses. No mutations were found. These results, together with our previous observations of a relative lack of Ki-ras gene mutations in the same tumors, are similar to those found in human UC-associated colon cancer, suggest a common pathway in these two systems, although they are different in their implication of p53 mutations. Therefore, this model may have some relevance and application to the study of colon cancer in human inflammatory bowel disease, which is not associated with APC mutations or with Ki-ras or p53 mutations.
Suzui
M
M
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Ushijima
T
T
Yoshimi
N
N
Nakagama
H
H
Hara
A
A
Sugimura
T
T
Nagao
M
M
Mori
H
H
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D001483:Base Sequence; D002273:Carcinogens; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000235:genetics*; D017931:DNA Primers; D004195:Disease Models, Animal; D017491:Genes, APC; D011905:Genes, ras; D006801:Humans; D008297:Male; D008746:Methylazoxymethanol Acetate; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D051381:Rats; D011916:Rats, Inbred F344
D000880:Anthraquinones; D002273:Carcinogens; D017931:DNA Primers; D008746:Methylazoxymethanol Acetate; C061208:1-hydroxyanthraquinone