Correlation of (6-4)photoproduct formation with transforming mutations in UV-irradiated Ha-ras.
Sites and types of mutations in relation to the amount of cyclobutane pyrimidine dimers (CPDs) and (6-4)-photoproducts in UV-irradiated normal Ha-ras sequences were investigated. Mouse BALB/C 3T3 cells were transfected with UV-irradiated pYN-mHras plasmids containing mouse normal Ha-ras sequences, and transformed foci developed. Direct DNA sequencing of the Ha-ras retrieved from the foci revealed that most mutations (23/24, 96%) took place at dipyrimidine sequences, and the C-->T transition at the 3'-cytosine in 5'-TC or 5'-CC sequences was predominant (17/24, 71%) in codons 12, 13 and 60. In codon 61, where 5'-TC or 5'-CC is absent, two mutations were found at the 5'-TT sequence. More (6-4)photoproducts were produced than CPDs in codons 12, 13 and 60, and more CPDs were produced than (6-4)photoproducts in codon 61. These results suggest that (6-4)photoproducts are the major lesion leading to the mutations in the mouse Ha-ras sequence and subsequent transformation of BALB/C 3T3 cells.
Yagi
T
T
Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Japan.
Morimoto
T
T
Takebe
H
H
D016475:3T3 Cells / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D011905:Genes, ras / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D010777:Photochemistry; D010957:Plasmids / Q000235:genetics / Q000528:radiation effects; D011740:Pyrimidine Dimers / Q000378:metabolism; D014162:Transfection; D014170:Transformation, Genetic / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D011740:Pyrimidine Dimers; D004247:DNA