Correlations of DNA strand breaks and their repair with cell survival following acute exposure to mercury(II) and X-rays

O Cantoni and M Costa

Alkaline elution analysis demonstrates that both HgCl2 and X-rays result in a rapid induction of DNA single-strand breaks at acutely cytotoxic doses (HgCl2, 25-100 microM for 60 min; X-rays, 150-600 rads) in cultured Chinese hamster ovary cells. Cytotoxicity, as measured by cell-plating efficiency, correlates linearly with the level of DNA breakage induced by both agents (HgCl2, r = 0.97; X-rays, r = 0.99), although a substantial difference in axis intercepts of the two linear regression lines indicates that a higher level of DNA damage was required by X-rays as compared with HgCl2 to produce an equivalent level of cell killing. DNA damage induced by X-rays was rapidly repaired such that within 1 hr following treatment the elution rate of DNA from treated cells resembled that obtained in untreated cultures. In contrast, DNA damage after Hg2+ insult was not repaired, and further damage was evident following a similar 1-hr recovery period. Addition of noncytotoxic, non-DNA-damaging concentrations of HgCl2 (10 microM) to cells 15-45 min following treatment with X-rays greatly inhibited the repair of the DNA strand breaks. Thus, although both HgCl2 and X- rays induce rapid and striking single-strand breaks in the DNA, persistence of Hg2+ in the cell can inhibit the repair of these breaks. The inhibition of DNA repair by HgCl2 may explain why this agent is not severely mutagenic or carcinogenic despite its ability to induce an X- ray-like DNA damage and why a lower level of mercury-induced DNA damage, compared with that induced by X-rays, was required to produce an equivalent level of cell death.

Volume 24, Issue 1, pp. 84-89, 07/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics