Effects of N-methyl-N'-nitro-N-nitrosoguanidine on the human colorectal polyps consecutively maintained in SCID mice.
N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatments for a long period induced morphological and molecular alterations in the benign human colorectal polyps which were maintained in the severe combined immunodeficient C.B17/N-scid/scid mice. Thirty four xenografts of colorectal polyps from five solitary polyp and three familial polyposis patients were examined for K-ras and p53 mutations. Six K-ras mutations were induced in 16 grafts treated with MNNG more than five times, while no K-ras mutations were detected in 14 untreated grafts (P<0.05). Additional and new K-ras mutations were also induced in two polyps in which K-ras mutation had pre-existed. p53 mutations were not observed in both MNNG-treated and untreated groups. The mutations in K-ras gene were induced at codon 12 (GGT-->GAT) except one at codon 13 (GGC-->GGT). The results indicate that K-ras mutation plays an important role in human colorectal carcinogenesis as is the case in experimental animals.
Taniguchi
E
E
Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, 2-2 Yamada-Oka, Suita, Osaka 565-0871, Japan. tnomura@radbio.med.osaka-u.ac.jp
Nakajima
H
H
Hongyo
T
T
Fukuda
K
K
Li
L Y
LY
Kurooka
M
M
Matsuda
H
H
Nomura
T
T
D000818:Animals; D003062:Codon / Q000187:drug effects / Q000235:genetics; D003111:Colonic Polyps / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D016158:Genes, p53 / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D051379:Mice; D016513:Mice, SCID; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013997:Time Factors; D014183:Transplantation, Heterologous
D003062:Codon; D009153:Mutagens; D008769:Methylnitronitrosoguanidine