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. 1994 Sep;102(Suppl 3):51–55. doi: 10.1289/ehp.94102s351

Effects of metal treatment on DNA repair in polyamine-depleted HeLa cells with special reference to nickel.

R D Snyder 1
PMCID: PMC1567407  PMID: 7843137

Abstract

Human cells depleted of the naturally occurring polyamines putrescine, spermidine, and spermine exhibit altered chromatin structure and marked deficiencies in DNA replicative and repair processes. Similar effects have been observed following treatment of normal mammalian cells with various heavy metal salts. In an attempt to better understand how metals interfere with normal DNA metabolic processes, a series of studies was carried out in which the toxicity and repair-inhibitory properties of various metals were evaluated in polyamine-depleted HeLa cells. Cytotoxicity of copper, zinc, magnesium, and cadmium was not altered in cells carrying lower polyamine pools. However, the sensitivity to nickel was markedly increased upon polyamine depletion, a condition that was readily reversed by polyamine supplementation. Nucleoid sedimentation analysis indicated that a greater amount of nickel-induced DNA damage occurred in polyamine-depleted cells than in normal cells, possibly serving as the basis for the increased sensitivity. Both polyamine depletion and nickel treatment result in decreased repair of DNA strand breaks and decreased cloning efficiency following X-ray and ultraviolet irradiation. Nickel treatment of polyamine-depleted cells resulted in synergistic sensitivity to both radiation treatments. None of the other metals tested enhanced X-ray or ultraviolet sensitivity of polyamine-depleted cells. Analysis of retarded repair sites following ultraviolet irradiation indicated those sites to be nonligatable in polyamine-depleted and nickel-treated cells, suggesting a block in the normal gap-sealing process.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bowlin T. L., McKown B. J., Sunkara P. S. Ornithine decarboxylase induction and polyamine biosynthesis are required for the growth of interleukin-2- and interleukin-3-dependent cell lines. Cell Immunol. 1986 Apr 1;98(2):341–350. doi: 10.1016/0008-8749(86)90294-7. [DOI] [PubMed] [Google Scholar]
  2. Cleaver J. E. Specificity and completeness of inhibition of DNA repair by novobiocin and aphidicolin. Carcinogenesis. 1982;3(10):1171–1174. doi: 10.1093/carcin/3.10.1171. [DOI] [PubMed] [Google Scholar]
  3. Cook P. R., Brazell I. A. Detection and repair of single-strand breaks in nuclear DNA. Nature. 1976 Oct 21;263(5579):679–682. doi: 10.1038/263679a0. [DOI] [PubMed] [Google Scholar]
  4. Danzin C., Marchal P., Casara P. Irreversible inhibition of rat S-adenosylmethionine decarboxylase by 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine. Biochem Pharmacol. 1990 Oct 1;40(7):1499–1503. doi: 10.1016/0006-2952(90)90446-r. [DOI] [PubMed] [Google Scholar]
  5. Hartwig A., Beyersmann D. Comutagenicity and inhibition of DNA repair by metal ions in mammalian cells. Biol Trace Elem Res. 1989 Jul-Sep;21:359–365. doi: 10.1007/BF02917276. [DOI] [PubMed] [Google Scholar]
  6. Hartwig A., Beyersmann D. Enhancement of UV-induced mutagenesis and sister-chromatid exchanges by nickel ions in V79 cells: evidence for inhibition of DNA repair. Mutat Res. 1989 Jan;217(1):65–73. doi: 10.1016/0921-8777(89)90037-2. [DOI] [PubMed] [Google Scholar]
  7. Kleppe K., Osland A., Fosse V., Male R., Lossius I., Helland D., Lillehaug J. R., Raae A. J., Kleppe R. K., Nes I. F. Effect of polyamines on enzymes involved in DNA repair. Med Biol. 1981 Dec;59(5-6):374–380. [PubMed] [Google Scholar]
  8. Sen P., Conway K., Costa M. Comparison of the localization of chromosome damage induced by calcium chromate and nickel compounds. Cancer Res. 1987 Apr 15;47(8):2142–2147. [PubMed] [Google Scholar]
  9. Sen P., Costa M. Induction of chromosomal damage in Chinese hamster ovary cells by soluble and particulate nickel compounds: preferential fragmentation of the heterochromatic long arm of the X-chromosome by carcinogenic crystalline NiS particles. Cancer Res. 1985 May;45(5):2320–2325. [PubMed] [Google Scholar]
  10. Sen P., Costa M. Pathway of nickel uptake influences its interaction with heterochromatic DNA. Toxicol Appl Pharmacol. 1986 Jun 30;84(2):278–285. doi: 10.1016/0041-008x(86)90135-3. [DOI] [PubMed] [Google Scholar]
  11. Snyder R. D., Davis G. F., Lachmann P. J. Inhibition by metals of X-ray and ultraviolet-induced DNA repair in human cells. Biol Trace Elem Res. 1989 Jul-Sep;21:389–398. doi: 10.1007/BF02917280. [DOI] [PubMed] [Google Scholar]
  12. Snyder R. D. Inhibition of X-ray-induced DNA strand break repair in polyamine-depleted HeLa cells. Int J Radiat Biol. 1989 May;55(5):773–782. doi: 10.1080/09553008914550821. [DOI] [PubMed] [Google Scholar]
  13. Snyder R. D., Lachmann P. J. Thiol involvement in the inhibition of DNA repair by metals in mammalian cells. Mol Toxicol. 1989 Apr-Jun;2(2):117–128. [PubMed] [Google Scholar]
  14. Snyder R. D. Polyamine depletion is associated with altered chromatin structure in HeLa cells. Biochem J. 1989 Jun 15;260(3):697–704. doi: 10.1042/bj2600697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Snyder R. D., Sunkara P. S. Effect of polyamine depletion on DNA damage and repair following UV irradiation of HeLa cells. Photochem Photobiol. 1990 Sep;52(3):525–532. doi: 10.1111/j.1751-1097.1990.tb01795.x. [DOI] [PubMed] [Google Scholar]

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