Mutations induced by DNA lesions in hot spots of the c-Ha-ras gene.
In order to investigate whether several DNA lesions (O6-methylguanine, 8-hydroxyguanine, xanthine, an abasic site analogue and hypoxanthine) activate a c-Ha-ras gene and to determine the type of mutations induced by the DNA lesions, they were introduced into a synthetic c-Ha-ras gene by DNA cassette mutagenesis techniques. The modified genes were transfected into mouse NIH3T3 cells and the c-Ha-ras genes present in transformed cells were analysed. O6-methylguanine and xanthine induced a mutation to A, hypoxanthine induced a mutation to G. 8-hydroxyguanine and the abasic site analogue caused random mutations in the modified and adjacent positions. These results indicated that the synthetic c-Ha-ras gene is very useful for the detection of mutations caused by a DNA lesion.
Kamiya
H
H
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Miura
H
H
Suzuki
M
M
Murata
N
N
Ishikawa
H
H
Shimizu
M
M
Komatsu
Y
Y
Murata
T
T
Sasaki
T
T
Inoue
H
H
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004249:DNA Damage; D011905:Genes, ras; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D019820:Xanthine; D014970:Xanthines / Q000737:chemistry
D007042:Hypoxanthines; D014970:Xanthines; D019820:Xanthine; D019271:Hypoxanthine; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; C008449:O-(6)-methylguanine