Frequent mutations of Ki-ras codon 12 in N-bis (2-hydroxypropyl)-nitrosamine-initiated thyroid, kidney and lung tumors in Wistar rats.
N-Bis (2-hydroxypropyl) nitrosamine (DHPN) is a very potent mutagen and wide spectrum carcinogen in rodents. In the present study, we investigated mutational activation of the Ki-ras gene in eight thyroid, five kidney (four mesenchymal and one transitional cell lesion) and two lung tumors induced with DHPN. Mutations were identified using single-strand conformation polymorphism, restriction fragment length polymorphism and DNA sequencing analysis. All of the 15 neoplasms could be shown to have mutations in codon 12 (GGT-->GAT). These results suggest that Ki-ras mutations are frequent events during the development of DHPN-induced carcinomas in these organs. In a separate experiment, moreover, we analyzed the presence of Ki-ras mutations in various tissues 8 weeks after DHPN treatment. One of five thyroid tissues treated with DHPN was found to have the same characteristic mutation, suggesting that it may represent an early event during carcinogen-induced tumor formation in the thyroid.
Kitahori
Y
Y
Second Department of Pathology, Nara Medical University, Japan.
Naito
H
H
Konishi
N
N
Ohnishi
T
T
Shirai
T
T
Hiasa
Y
Y
D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D003062:Codon; D017931:DNA Primers; D015252:Deoxyribonucleases, Type II Site-Specific; D011905:Genes, ras / Q000187:drug effects*; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D009602:Nitrosamines / Q000633:toxicity*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D051381:Rats; D017208:Rats, Wistar; D013964:Thyroid Neoplasms / Q000139:chemically induced / Q000235:genetics*
D002273:Carcinogens; D003062:Codon; D017931:DNA Primers; D009153:Mutagens; D009602:Nitrosamines; C012457:diisopropanolnitrosamine; D015252:Deoxyribonucleases, Type II Site-Specific; C024412:GGTGA-specific type II deoxyribonucleases