Correlations of DNA strand breaks and their repair with cell survival following acute exposure to mercury(II) and X-rays
Alkaline elution analysis demonstrates that both HgCl/sub 2/ and X-rays result in a rapid induction of DNA single-strand breaks at acutely cytotoxic doses (HgCl/sub 2/, 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 (HgCl/sub 2/, 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 HgCl/sub 2/ 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 Hg/sup 2 +/ insult was not repaired, and further damage was evident following a similar 1-hr recovery period. Addition of noncytotoxic, non-DNA-damaging concentrations of HgCl/sub 2/ (10 microM) to cells 15-45 min following treatment with X-rays greatly inhibited the repair of the DNA strand breaks. Thus, although both HgCl/sub 2/ and X-rays induce rapid and striking single-strand breaks in the DNA, persistence of Hg/sup 2 +/ in the cell can inhibit the repair of these breaks. The inhibition of DNA repair by HgCl/sub 2/ 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.
- Research Organization:
- Univ. of Texas, Medical School, Houston
- OSTI ID:
- 7013526
- Journal Information:
- Mol. Pharmacol.; (United States), Vol. 24:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
CELL KILLING
RADIOINDUCTION
MERCURY CHLORIDES
BIOLOGICAL EFFECTS
STRAND BREAKS
BIOLOGICAL REPAIR
DNA
FIBROBLASTS
HAMSTERS
SURVIVAL CURVES
X RADIATION
ANIMAL CELLS
ANIMALS
BIOLOGICAL RECOVERY
CHLORIDES
CHLORINE COMPOUNDS
CONNECTIVE TISSUE CELLS
ELECTROMAGNETIC RADIATION
HALIDES
HALOGEN COMPOUNDS
IONIZING RADIATIONS
MAMMALS
MERCURY COMPOUNDS
MERCURY HALIDES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
RADIATIONS
RECOVERY
REPAIR
RODENTS
SOMATIC CELLS
VERTEBRATES
560121* - Radiation Effects on Cells- External Source- (-1987)
560301 - Chemicals Metabolism & Toxicology- Cells- (-1987)
550300 - Cytology