c-Ha-ras containing 8-hydroxyguanine at codon 12 induces point mutations at the modified and adjacent positions.
To determine the type of mutation induced by 8-hydroxyguanine in a mammalian system, we examined the mutations induced by a synthetic c-Ha-ras protooncogene containing 8-hydroxyguanine in the second position of codon 12 (GGC) in NIH3T3 cells. Transfection of this gene significantly increased the number of transformed foci. The c-Ha-ras gene present in these foci was analyzed by the polymerase chain reaction-restriction enzyme method. Interestingly, sequence analysis revealed random mutations at the modified site (G----T, G----A, and G----C) as well as mutations of the adjacent G on the 5'-side of 8-hydroxyguanine (G----A and G----T).
Kamiya
H
H
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Miura
K
K
Ishikawa
H
H
Inoue
H
H
Nishimura
S
S
Ohtsuka
E
E
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D003062:Codon / Q000235:genetics*; D004252:DNA Mutational Analysis; D011905:Genes, ras / Q000235:genetics*; D006147:Guanine / Q000031:analogs & derivatives* / Q000633:toxicity; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014162:Transfection
D003062:Codon; C024829:8-hydroxyguanine; D006147:Guanine