Abstract

The effect of relatively nontoxic levels of HgCl2 on semiconservative DNA synthesis and on DNA repair induced following treatment of intact cells with X-ray or ultraviolet (UV) light has been studied in cultured Chinese hamster ovary cells. In the presence of 1 microM HgCl2 the repair of DNA strand breaks induced by 450 rads of X-rays was reduced by 37%. If a treatment of 2.5 microM HgCl2 was given to cells for only 15 min prior to a 450-rad irradiation, the rate of repair was reduced even further with only 25% of the breaks being repaired in the first hour following irradiation. When comparable treatments of HgCl2 were given to Chinese hamster ovary cells in conjunction with UV irradiation there was no significant effect on either the number of initial strand scission events or the return to high molecular weight DNA following completion of repair. Only after exposure of cells to toxic levels of Hg(II) (higher concentrations or longer treatments) was there measurable inhibition of UV-induced repair as evidenced by a reduced rate of ligation of DNA to a high molecular weight form. Inhibition of the endonuclease step of UV repair was not observed since Hg(II)-treated cells exhibited the same level of strand scission immediately following UV as cells not treated with Hg(II). The observed differences in the effects of Hg(II) on two pathways for DNA repair indicate that the potential for synergistic action between Hg(II) and other DNA damaging agents will be determined in part by the repair pathways induced by each agent. Additionally, it was found that inhibition of semiconservative synthesis also occurs at low concentrations of HgCl2 similar to those affecting X-ray-induced repair. The presence of Hg-DNA adducts in the DNA at these concentrations may cause a reduction in normal replication to facilitate DNA repair.