Application of the restriction site mutation technique to N-methyl-N-nitrosourea-induced mutations in the rat

作者：Suzen S; Jenkins GJS; Parry JM^*

来源：Teratogenesis, Carcinogenesis, and Mutagenesis, 1998, 18(4): 171-182.

DOI：10.1002/(SICI)1520-6866(1998)18:4<171::AID-TCM3>3.3.CO;2-E

• mutation
• MNU
• RSM assay
• mutation frequency
• H-ras gene
• p53 gene

The restriction site mutation (RSM) assay was developed in this laboratory for the detection of point mutations that occur within restriction endonuclease recognition sequences in the genomic DNA of the rat. Mutations were detected and identified in a number of tissues from N-methyl-N-nitrosourea (MNU)-treated rats. Resistant restriction enzyme products were detected in 5 of the 13 restriction endonuclease recognition sequences tested (NcoI, BslI, CfoI, DdeI, and HindIII). These mutations were detected in the p53 tumor suppressor gene and the H-ras protooncogene. No resistant RSM products were detected in any of the samples taken from untreated animals. The MNU-induced mutations were identified as G to A and A to G transitions. Our results describe the first successful application of the RSM assay in detecting induced mutations in the rat acid highlight the usefulness of the RSM assay in the analysis of mutagen-induced base changes without the requirement for selection of a mutant phenotype. Given the increasing use of the rat as an animal model in genotoxicity studies, the development of such tests is essential for future genotoxicity investigations. Teratogenesis Carcinog. Mutagen. 18:171-182, 1998.

• 出版日期1998