EXPRESSION OF THE ESCHERICHIA-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 C 8-oxoGuanine residues from gamma-irradiated DNA. The fpg gene was liga ted in the psV2 vector and transfected into the Chinese hamster CHO an d V-79 cells. The transfected cells expressed a formamido-pyrimidine-D NA-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 w as similar in control and transfected cells. Furthermore CHO cells exp ressing the fpg gene had the same resistance to the lethal effect of h ydrogen peroxide as control cells. However,the sensitivity to the muta genic effect of gamma-rays, measured as B-thioguanine resistance, decr eased 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-oxo guanine.