No involvement of Ki-ras or p53 gene mutations in colitis-associated rat colon tumors induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate.
1-Hydroxyanthraquinone (1-HA), which is present in some herbs, and methylazoxymethanol (MAM) acetate, a metabolite of azoxymethane, show synergistic carcinogenicity in rat colon, and 1-HA induces ulcerative changes with simultaneous severe inflammation of the entire colon. In this study, mutations in Ki-ras (exons 1 and 2) and p53 (exons 4-7) were studied by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Of 18 adenomas and 38 adenocarcinomas induced in male F344 rats (52 tumors induced by 1-HA plus MAM acetate, three by 1-HA alone, and one by MAM acetate alone), no mutations in Ki-ras or p53 were detected under two conditions of PCR-SSCP analysis. Because human colon carcinomas from patients with ulcerative colitis have a very low incidence of Ki-ras mutation, this experimental system would be a good animal model of human colon carcinomas with ulcerative colitis and of human colon carcinomas without Ki-ras or p53 mutations.
Suzui
M
M
First Department of Pathology, Gifu University School of Medicine, Japan.
Yoshimi
N
N
Ushijima
T
T
Hirose
Y
Y
Makita
H
H
Wang
A
A
Kawamori
T
T
Tanaka
T
T
Mori
H
H
Nagao
M
M
D000818:Animals; D000880:Anthraquinones; D001483:Base Sequence; D003062:Codon; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000235:genetics*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D005091:Exons; D016158:Genes, p53; D011905:Genes, ras; D008297:Male; D008746:Methylazoxymethanol Acetate; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344
D000880:Anthraquinones; D003062:Codon; D017931:DNA Primers; D008746:Methylazoxymethanol Acetate; C061208:1-hydroxyanthraquinone