Expression of the E. coli fpg gene in mammalian cells reduces the mutagenicity of gamma-rays.
The E. coli fpg gene encodes the formamido-pyrimidine-DNA-glycosylase (FPG protein) which specifically removes the formamido-pyrimidine and C8-oxoGuanine residues from gamma-irradiated DNA. The fpg gene was ligated in the psV2 vector and transfected into the Chinese hamster CHO and V-79 cells. The transfected cells expressed a formamido-pyrimidine-DNA-glycosylase activity 30 to 40-fold over the constitutive level. The resistance of CHO and V-79 cells to the lethal effect of gamma-rays was similar in control and transfected cells. Furthermore CHO cells expressing the fpg gene had the same resistance to the lethal effect of hydrogen peroxide as control cells. However, the sensitivity to the mutagenic effect of gamma-rays, measured as 6-thioguanine resistance, decreased both in CHO and V-79 transfected cells. Since the lethal effect of gamma-rays was not modified in cells overproducing the FPG protein, the results suggest that this protein protects the cells against the mutagenic lesions formed by ionizing radiations, and among them C8-oxoguanine.
Laval
F
F
Groupe Radiochimie de l'ADN, U 247 INSERM, Institut Gustave Roussy, Villejuif, France.
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins; D005720:Gamma Rays; D015870:Gene Expression; D005798:Genes, Bacterial / Q000502:physiology; D006147:Guanine / Q000031:analogs & derivatives; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009699:N-Glycosyl Hydrolases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011836:Radiation Tolerance / Q000235:genetics*
D029968:Escherichia coli Proteins; D006147:Guanine; D006861:Hydrogen Peroxide; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli