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SnCl2-induced DNA damage and repair inhibition of MMS-caused lesions in V79 Chinese hamster fibroblasts

  • Genotoxicity and Carcinogenicity
  • Published:
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Abstract

In order to clarify the molecular mechanisms of Sn2+ genotoxicity, we evaluated the induction of strand breaks, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (Endo III) sensitive sites, and the interference with the repair of methyl methane sulfonate (MMS)-caused DNA damage in V79 Chinese hamster lung fibroblasts exposed to stannous chloride by comet assay. A concentration-related increase in the DNA damage induced by 2 h SnCl2 treatment at a concentration range of 50–1,000 μM was observed (r = 0.993; P < 0.01). Significantly elevated DNA migration in relation to the control level was detected at doses 100, 500 and 1,000 μM in normal alkaline and at doses 500 and 1,000 μM in modified (with Fpg and Endo III) comet assay. Although 50 μM SnCl2 concentration did not increase significantly the DNA migration by itself in comet assay, it was capable to inhibit the repair of MMS-induced DNA damage during the post-treatment period of 24 h. Our results demonstrate the genotoxic and comutagenic effects of stannous chloride in V79 cells. The inhibitory effect of Sn2+ on repair of MMS-induced DNA damage suggests that this metal can also interfere in DNA repair systems thus contributing to increased mutation by shifting the balance from error-free to error-prone repair processes.

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Abbreviations

8-oxoG:

8-Oxo-7,8-dihydroguanine

AP sites:

Apurinic/apyrimidinic sites

BER:

Base excision repair

Endo III:

Endonuclease III

Fpg:

Formamidopyrimidine DNA glycosylase

MMS:

Methyl methane sulfonate

ROS:

Reactive oxygen species

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Acknowledgments

Research supported by Fundação de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and GENOTOX, Royal Institute. C. M. Viau held a CNPq fellowship and is a Ph.D. student from UFRGS, T. N. Guecheva is supported by CNPq, C. Pungartnik held a fellowship by CNPq (PRODOC/FAPESB/CNPq) and M. Brendel is Visiting Scientist at UESC supported by Fundação de Amparo a Pesquisa do Estado da Bahia (FAPESB).

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Authors and Affiliations

  1. Departamento de Biofísica/Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, UFRGS, Av. Bento Gonçalves 9500, Porto Alegre, 91501-970, Brazil

    C. M. Viau, Temenouga N. Guecheva, F. G. Sousa, J. Saffi & João Antonio Pêgas Henriques

  2. Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz, UESC, Ilhéus, BA, Brazil

    C. Pungartnik & M. Brendel

  3. Laboratório de Genética Toxicológica, Universidade Luterana do Brasil, Canoas, RS, Brazil

    J. Saffi & João Antonio Pêgas Henriques

  4. Instituto de Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, RS, Brazil

    João Antonio Pêgas Henriques

Authors
  1. C. M. Viau
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  2. Temenouga N. Guecheva
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  3. F. G. Sousa
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  4. C. Pungartnik
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  5. M. Brendel
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  6. J. Saffi
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  7. João Antonio Pêgas Henriques
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Correspondence to João Antonio Pêgas Henriques.

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Viau, C.M., Guecheva, T.N., Sousa, F.G. et al. SnCl2-induced DNA damage and repair inhibition of MMS-caused lesions in V79 Chinese hamster fibroblasts. Arch Toxicol 83, 769–775 (2009). https://doi.org/10.1007/s00204-009-0409-z

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  • DOI: https://doi.org/10.1007/s00204-009-0409-z

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