Expression of the E.coli fpg gene in mammalian cells reduces the mutagenicity of γ-rays

摘要

The E.coli fpg gene encodes the formamido-pyrimidine- DNA-glycosylase (FPG protein) which specifically removes the formamido-pyrimidine and C8-oxoGuanine residues from γ-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-DNAglycosylase activity 30 to 40-fold over the constitutive level. The resistance of CHO and V-79 cells to the lethal effect of γ-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 γ-rays, measured as 6-thioguanine resistance, decreased both in CHO and V-79 transfected cells. Since the lethal effect of γ-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.