Differential ability of polymorphic OGG1 proteins to suppress mutagenesis induced by 8-hydroxyguanine in human cell in vivo.
OGG1 protein has an ability to suppress mutagenesis induced by 8-hydroxyguanine (8OHG), an oxidatively damaged promutagenic base. Here, the mutation suppressive ability was compared between two common polymorphic OGG1 proteins, OGG1-Ser326 and OGG1-Cys326, using a supF forward mutation assay employing an 8OHG-containing plasmid. Polymorphic OGG1 proteins were exogenously expressed by adenoviral transduction in H1299 human lung cancer cells, in which endogenous OGG1 protein was undetectable by western blot analysis. Mutations by 8OHG were more efficiently suppressed in OGG1-Ser326 transduced cells than OGG1-Cys326 transduced cells. The results indicated that OGG1-Cys326 has a lower ability to prevent mutagenesis by 8OHG than OGG1-Ser326 in vivo in human cells; supporting the results of recent association studies that OGG1-Cys326 is a risk allele for several types of human cancers.
Yamane
Arito
A
Biology Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Kohno
Takashi
T
Ito
Kohei
K
Sunaga
Noriaki
N
Aoki
Kazunori
K
Yoshimura
Kimio
K
Murakami
Hirokazu
H
Nojima
Yoshihisa
Y
Yokota
Jun
J
D000256:Adenoviridae / Q000235:genetics; D015153:Blotting, Western; D045647:DNA Glycosylases / Q000502:physiology*; D016153:Genes, Suppressor; D006147:Guanine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012343:RNA, Transfer / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
C096275:supF tRNA; C024829:8-hydroxyguanine; D006147:Guanine; D012343:RNA, Transfer; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human