Frequent mutations of Ki-ras codon 12 in N-bis (2-hydroxypropyl)-nitrosamine-initiated thyroid, kidney and lung tumors in Wistar rats.

Abstract

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.

• Authors: Y Kitahori, H Naito, N Konishi, T Ohnishi, T Shirai, Y Hiasa
• Journal: Cancer letters (Cancer Lett) Vol. 96 Issue 2 Pg. 155-61 (Sep 25 1995) ISSN: 0304-3835 [Print] Ireland
• PMID: 7585451 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Codon
• DNA Primers
• Mutagens
• Nitrosamines
• diisopropanolnitrosamine
• Deoxyribonucleases, Type II Site-Specific
• GGTGA-specific type II deoxyribonucleases

Topics

• Animals
• Base Sequence
• Carcinogens (toxicity)
• Codon
• DNA Primers
• Deoxyribonucleases, Type II Site-Specific
• Genes, ras (drug effects)
• Kidney Neoplasms (chemically induced, genetics)
• Lung Neoplasms (chemically induced, genetics)
• Male
• Molecular Sequence Data
• Mutagenesis
• Mutagens (toxicity)
• Nitrosamines (toxicity)
• Point Mutation
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Rats
• Rats, Wistar
• Thyroid Neoplasms (chemically induced, genetics)