Biological Trace Element Research

, Volume 130, Issue 3, pp 249–261 | Cite as

Mutagenic and Genotoxic Effects of cis-(Dichloro)tetraammineruthenium(III) Chloride on Human Peripheral Blood Lymphocytes

  • Alessandra de Santana Braga Barbosa Ribeiro
  • Cláudio Carlos da Silva
  • Flávia de Castro Pereira
  • Aliny Pereira de Lima
  • Cesar Augusto Sam Tiago Vilanova-Costa
  • Simone Santos Aguiar
  • Luiz Alfredo Pavanin
  • Aparecido Divino da Cruz
  • Elisângela de Paula Silveira-Lacerda
Article
First Online:
Received:
Accepted:

Abstract

Chemotherapeutic agents play an important role in cancer treatment mostly due their systemic action on human organism allowing access to liquid tumors and even metastases. Among these drugs, ruthenium compounds have been showing promising results to treat tumors and represent an important development of new antitumor therapy. This study presents the evaluation of cis-(dichloro)tetraammineruthenium(III) chloride, cis-[RuCl2(NH3)4]Cl, genotoxic effects using human peripheral blood lymphocytes cultured in vitro. Mitotic index (MI), chromosome aberrations (CA), and DNA damage using the comet assay were analyzed. MI in human peripheral blood lymphocyte cultures treated with 1, 10, 100, and 1,000 μg mL−1 cis-[RuCl2(NH3)4]Cl were 5.9%, 4.6%, 3.9%, and 0%, respectively. Doxorubicin chloridate was used as the positive control. CA derived from 1, 10, and 100 μg mL−1 concentrations were defined as spontaneous when compared with the negative control, and at the concentration of 1,000 μg mL−1, the cell cycle was inhibited (IM = 0%). Results obtained for the comet assay using cis-[RuCl2(NH3)4]Cl suggest that this compound has no genotoxic activity against cultured human peripheral blood lymphocytes.

Keywords

Cancer cis-(Dichloro)tetraammineruthenium(III) chloride Mitotic index Chromosome aberrations Comet assay 
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Notes

Acknowledgments

This work was supported by Research and Projects Financing (FINEP) (grant no. 01.06.0941.00/CT-Saúde to Elisângela de Paula Silveira-Lacerda), by Coordination for the Advancement of Higher Education Staff (CAPES) through a fellowship to Alessandra de Santana Braga Barbosa Ribeiro, and by Brazilian National Counsel of Technological and Scientific Development (CNPq) through fellowships to Flávia de Castro Pereira (grant no. 381302/2007-5), Cesar Augusto Sam Tiago Vilanova-Costa (grant no. 381303/2007-1), and Aliny Pereira de Lima (grant no. 370646/2007-0).

Funding sources

There are not any financial or personal interests that might be viewed as an inappropriate influence to work presented. The attached manuscript, “Mutagenic and genotoxic effects of cis-(dichloro)tetraammineruthenium(III) chloride on human peripheral blood lymphocytes,” was completely financed by governmental and nonprofit institutions, Brazilian National Counsel of Technological and Scientific Development (CNPq), Research and Projects Financing (FINEP), and Coordination for the Advancement of Higher Education Staff (CAPES).

References

  1. 1.
    C.S. Allardyce and P.J. Dyson, Ruthenium in medicine: current clinical uses and future prospects, Plat. Met. Rev. 45, 6–69 (2001).Google Scholar
  2. 2.
    A. Cuin, A.C. Massabni, C.Q.F. Leite, D.N. Sato, A. Neves, B. Szpoganicz, M.S. Silva and A.J. Bortoluzzi, Synthesis, X-ray structure and antimycobacterial activity of silver complexes with a-hydroxycarboxylic acids, J. Inorg. Biochem. 101, 291–296 (2007).PubMedCrossRefGoogle Scholar
  3. 3.
    V. Brabec and O. Nováková, DNA binding mode of ruthenium complexes and relationship to tumor cell toxicity, Drug Resist. Updat. 9, 111–122 (2006).PubMedCrossRefGoogle Scholar
  4. 4.
    G. Sava, S. Pacor, F. Bregant, V. Ceschia and G. Mestroni, Metal complexes of ruthenium: antineoplastic properties and perspectives, Anti-cancer Drugs 1, 99–108 (1990).PubMedCrossRefGoogle Scholar
  5. 5.
    G. Sava and A. Bergamo, Ruthenium-based compounds and tumour growth control, Int. J. Oncol. 17, 353–365 (2000).PubMedGoogle Scholar
  6. 6.
    M.J. Clarke, Ruthenium metallopharmaceuticals, Coord. Chem. Rev 236, 209–233 (2003).CrossRefGoogle Scholar
  7. 7.
    M. Galanski, V.B. Arion, M.A. Jakupec and B.K. Keppler, Recent developments in the field of tumor-inhibiting metal complexes, Curr. Pharm. Des. 9, 2078–2089 (2003).PubMedCrossRefGoogle Scholar
  8. 8.
    E. Alessio, G. Mestroni, A. Bergamo and G. Sava, Ruthenium anticancer drugs, in: A. Sigel and H. Sigel (Eds.), Metal ions in biological systems. Metal complexes in tumor diagnosis and as anticancer agents, v. 42, Marcel Dekker, New York, pp. 323–351 (2004).Google Scholar
  9. 9.
    E. Alessio, G. Mestroni, A. Bergamo and G. Sava, Ruthenium antimetastatic agents, Curr. Top. Med. Chem. 4, 1525–1535 (2004).PubMedCrossRefGoogle Scholar
  10. 10.
    G. Sava, I. Capozzi, V. Clerici, G. Gagliardi, E. Alessio and G. Mestroni, Pharmacological control of lung metastases of solid tumours by a novel ruthenium complex, Clin. Exp. Metast. 16, 371–379 (1998).CrossRefGoogle Scholar
  11. 11.
    G. Sava, E. Alessio, A. Bergamo and G. Mestroni, Sulfoxide ruthenium complexes: non-toxic tools for the selective treatment of solid tumour metastases, in: M.J. Clarke and P.J. Sadler (Eds.), Topics in biological inorganic chemistry, v. 1, Springer, Berlin, pp. 143–169 (1999).Google Scholar
  12. 12.
    G. Sava, K. Clerici, I. Capozzi, M. Cocchietto, R. Gagliardi, E. Alessio, G. Mestroni and A. Perbellini, Reduction of lung metastasis by ImH[trans-RuCl4(DMSO)Im]: mechanism of the selective action investigated on mouse tumors, Anti Cancer Drugs 10, 129–138 (1999).PubMedCrossRefGoogle Scholar
  13. 13.
    G. Sava, R. Gagliardi, A. Bergamo, E. Alessio and G. Mestroni, Treatment of metastases of solid mouse tumours by NAMI-A: comparison with cisplatin, cyclophosphamide and dacarbazine, Anticancer Res. 19, 969–972 (1999).PubMedGoogle Scholar
  14. 14.
    A. Bergamo, S. Zorzet, B. Gava, A. Sorc, E. Alessio, E. Iengo and G. Sava, Effects of NAMI-A and some related ruthenium complexes on cell viability after short exposure of tumor cells, Anti Cancer Drugs 11, 667–672 (2000).Google Scholar
  15. 15.
    M. Cocchietto and G. Sava, Blood concentration and toxicity of the antimetastasis agent NAMI-A following repeated intravenous treatment in mice, Pharmacol. Toxicol. 87, 193–197 (2000).PubMedCrossRefGoogle Scholar
  16. 16.
    G. Sava and M. Cocchietto, Blood levels of ruthenium following repeated treatments with the antimetastatic compound NAMI-A in healthy beagle dogs, In Vivo 14, 741–744 (2000).PubMedGoogle Scholar
  17. 17.
    C.G. Hartinger, S. Zorbas-Seifried, M.A. Jakupec, B. Kynast, H. Zorbas and B.K. Keppler, From bench to bedside—preclinical and early clinical development of the anticancer agent indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019 or FFC14A), J. Inorg. Biochem. 100, 891–904 (2006).PubMedCrossRefGoogle Scholar
  18. 18.
    J.M. Rademaker-Lakhai, D. van den Bongard, D. Pluim, J.H. Beijnen and J.H.M. Schellens, A Phase I and pharmacological study with imidazolium-trans-DMSO-imidazole-tetrachlororuthenate, a novel ruthenium anticancer agent, Clin. Cancer Res. 10, 3717–3727 (2004).PubMedCrossRefGoogle Scholar
  19. 19.
    M.A. Jakupec, V.B. Arion, S. Kapitza, E. Reisner, A. Eichinger, M. Pongratz, B. Marian, N.G. von Keyserlingk and B.K. Keppler, KP1019 (FFC14A) from bench to bedside: preclinical and early clinical development: an overview, Int. J. Clin. Pharm. Ther. 43, 595–596 (2005).Google Scholar
  20. 20.
    C.E.S. Barbosa, Evaluation of acute toxicity and antitumor effect of cis-tetraammine(oxalato)ruthenium(III) dithionate in murine sarcoma 180. Master’s Thesis—Federal University of Goiás, Goiânia, Goiás, Brazil, 2007.Google Scholar
  21. 21.
    I. Kostova, Ruthenium complexes as anticancer agents, Curr Med Chem. 13, 1085–107 (2006).PubMedCrossRefGoogle Scholar
  22. 22.
    E.P. Silveira-Lacerda, Antitumoral evaluation of cis-[RuCl2(NH3)4]Cl using tumoral, human and mouse cells lineages. 67 f. Doctoral Thesis, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil, 2003.Google Scholar
  23. 23.
    C.S.R. Menezes, L.C.G.P. Costa, V. de M.R. Ávila, M.J. Ferreira, C.U. Vieira, L.A. Pavanin, M.I. Homsi-Brandeburgo, A. Hamaguchi and E.P. Silveira-Lacerda, Analysis in vivo of antitumor activity, cytotoxicity and interaction between plasmid DNA and the cis-dichlorotetraammineruthenium(III) chloride, Chemico-Biol. Int. 167, 116–124 (2007).CrossRefGoogle Scholar
  24. 24.
    E. Gebhart, L. Lösing and F. Wopfner, Chromosome studies on lymphocytes of patients under cytostatic therapy. I. Conventional chromosome studies in cytostatic interval therapy, Hum. Genet., 55, 53–63 (1980).CrossRefGoogle Scholar
  25. 25.
    B. Lambert, K. Holmberg and N. Einhorn, Persistence of chromosome rearrangements in peripheral lymphocytes from patients treated with melphalan for ovarian carcinoma, Hum. Genet. 67, 94–98 (1984).PubMedCrossRefGoogle Scholar
  26. 26.
    B. Lambert, K. Holmberg and N. Einhorn, Chromosomal damage and second malignancy in patients treated with melphalan, in: D. Schmahl and J.M. Kaldor (Eds.), Carcinogenicity of alkylating cytostatic drugs, IARC, Lyon, pp. 147–160 (1986).Google Scholar
  27. 27.
    S. Gundy, M. Baki, I. Bodrogi and A. Czeizel, Persistence of chromosomal aberrations in blood lymphocytes of testicular cancer patients. I. The effect of vinblastine, cisplatin and bleomycin adjuvant therapy, Oncology, 47, 410–414 (1990).CrossRefGoogle Scholar
  28. 28.
    A. Schinzel and W. Schmid, Lymphocyte chromosome studies in humans exposed to chemical mutagens. The validity of the method in 67 patients under cytostatic therapy, Mutat. Res. 40, 139–166 (1976).PubMedCrossRefGoogle Scholar
  29. 29.
    E. Weisburger, Bioassay program for carcinogenic hazards of cancer chemotherapeutic agents, Cancer 40, 1935–1949 (1977).PubMedCrossRefGoogle Scholar
  30. 30.
    C.C. Harris, A delayed complication of cancer therapy: cancer, J. Natl. Cancer Inst. 63, 275–277 (1979).PubMedGoogle Scholar
  31. 31.
    R.J. Albertini, D. Anderson, G.R. Douglas, L. Hagmar, K. Hemminki, F. Merlo, A.T. Natarajan, H. Norppa, D.E. Shuker, R. Tice, M.D. Waters and A. Aitio, IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. International Programme on Chemical Safety, Mutat. Res. 463, 111–172 (2000).PubMedCrossRefGoogle Scholar
  32. 32.
    R.R. Tice, E. Agurell, D. Anderson, B. Burlinson, A. Hartmann, H. Kobayashi, Y. Miyamae, E. Rojas, J.C. Ryu and Y.F. Sasaki, Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing, Environ. Mol. Mutagen. 35, 206–221 (2000).PubMedCrossRefGoogle Scholar
  33. 33.
    F. Faust, F. Kassie, S. Knasmüller, R.H. Boedecker, M. Mann and V. Mersch-Sundermann, The use of the alkaline comet assay with lymphocytes in human biomonitoring studies, Mutat. Res. 566, 209–229 (2004).PubMedCrossRefGoogle Scholar
  34. 34.
    L.A. Pavanin, E. Giesbrecht and E. Tfouni, Synthesis and properties of the ruthenium(I1) complexes cis-Ru(NH3)Isn)L2+. Spectra and reduction potentials, Inorganic Chemistry, 24 25, 4444–4446 (1985).CrossRefGoogle Scholar
  35. 35.
    P.S. Moorhead, P.C. Nowell, J. Mellman, D.M. Batipps and D.A. Hungerford, Chromosome preparations of leukocytes cultured from human peripheral blood, Exp. Cell Res. 20, 613–616 (1960).PubMedCrossRefGoogle Scholar
  36. 36.
    N.P. Singh, M.T. McCoy, R.R. Tice and E.L. Schneider, A simple technique for quantitation of low levels of DNA damage in individual cells, Exp. Cell Res. 175, 184–191 (1988).PubMedCrossRefGoogle Scholar
  37. 37.
    B. Burlinson, R.R. Tice, G. Speit, E. Agurell, S.Y. Brendler-Schwaab, A.R. Collins, P. Escobar, M. Honma, T.S. Kumaravel, M. Nakajima, Y.F. Sasaki, V. Thybaud, Y. Uno, M. Vasquez and A. Hartmann, Fourth international workgroup on genotoxicity testing: results of the in vivo comet assay workgroup, Mutat. Res. 627, 31–35 (2007).PubMedGoogle Scholar
  38. 38.
    R.L. Nussbaum, R.R. McInnes and H.F. Willard, Thompson & Thompson, Genetics in Medicine. 6th Ed. Philadelphia: Saunders; 2001.Google Scholar
  39. 39.
    T.H. Ochi-Lohmann, K. Okazaki, M.R. Madruga, C.A. Pereira, M.N. Rabello-Gay, Radiosensitivity of blood lymphocytes from basocellular carcinoma patients, as detected by the micronucleus assay, Mutat. Res. 357, 97–106 (1996).PubMedGoogle Scholar
  40. 40.
    P.L. Olive, G. Frazer and J.P. Banáth, Radiation-induced apoptosis measured in TK6 human B lymphoblast cells using the comet assay, Radiat. Res. 136, 130–136 (1993).PubMedCrossRefGoogle Scholar
  41. 41.
    R.M. Rosa, N.C. Hoch, G.V. Furtado, J. Saffi, J.A.P. Henriques, DNA damage in tissues and organs of mice treated with diphenyl diselenide, Mut. Res. 633, 35–45 (2007).Google Scholar
  42. 42.
    A.R. Trzeciak, J. Barnes and K.M. Evans, A modified alkaline comet assay for measuring DNA repair capacity in human population, Radiat. Res. 169, 110–121 (2008).PubMedCrossRefGoogle Scholar
  43. 43.
    F.C. Pereira, C.A.S.T. Vilanova-Costa, A.P. Lima, A.S.B.B. Ribeiro, H.D. da Silva, L.A. Pavanin and E.P. Silveira-Lacerda, Cytotoxic and genotoxic effects of cis-tetraammine(oxalato)ruthenium(III) dithionate on the root meristem cells of Allium cepa, Biol Trace Elem Res, doi: 10.1007/s12011-008-8272-y (2008).
  44. 44.
    R.A. Vilaplana, F. Delmani, C. Manteca, J. Torreblanca, J. Moreno, G. García-Herdugo and F. González-Vílchez, Synthesis, interaction with double-helical DNA and biological activity of the water soluble complex cis-dichloro-1,2-propylenediamine-N,N,N′N′-tetraacetato ruthenium (III) (RAP), J. Inorg. Biochem. 100, 1834–1841 (2006).PubMedCrossRefGoogle Scholar
  45. 45.
    A.M. Udayakumar and M. Krishna Bhargava, Persistence of chromosomal aberrations in blood lymphocytes 11 years after cessation of CMF therapy in a breast cancer patient, Cancer Letters 107, 1–3 (1996).PubMedCrossRefGoogle Scholar
  46. 46.
    K. Baria, C. Warren, S.A. Roberts, C.M. West and D. Scott, Chromosomal radiosensitivity as a marker of predisposition to common cancers? Br. J. Cancer 84, 892–896 (2001).PubMedCrossRefGoogle Scholar
  47. 47.
    A. Padjas, D. Lesisz, A. Lankoff, A. Banasik, H. Lisowska, R. Bakalarz, S. Góźdź and A. Wojcik, Cytogenetic damage in lymphocytes of patients undergoing therapy for small cell lung cancer and ovarian carcinoma, Toxicol. Appl. Pharmacol. 209, 183–191 (2005).PubMedCrossRefGoogle Scholar
  48. 48.
    H. Norppa, S. Bonassi, I.L. Hansteen, L. Hagmar, U. Strömberg, P. Rössner, P. Boffetta, C. Lindholm, S. Gundy, J. Lazutka, A. Cebulska-Wasilewska, E. Fabiánová, R.J. Srám, L.E. Knudsen, R. Barale and A. Fucic, Chromosomal aberrations and SCEs as biomarkers of cancer risk, Mutat. Res. 600, 37–45 (2006).PubMedGoogle Scholar
  49. 49.
    P. Boffetta, O. van der Hel, H. Norppa, E. Fabianova, A. Fucic, S. Gundy, J. Lazutka, A. Cebulska-Wasilewska, D. Puskailerova, A. Znaor, Z. Kelecsenyi, J. Kurtinaitis, J. Rachtan, A. Forni, R. Vermeulen and S. Bonassi, Chromosomal aberrations and cancer risk: results of a cohort study from Central Europe. International Agency for Research on Cancer, Lyon, Am. J. Epidemiol. 165, 36–43 (2007).PubMedCrossRefGoogle Scholar
  50. 50.
    N.I. Weijl, F.J. Cleton and S. Osanto, Free radicals and antioxidants in chemotherapy-induced toxicity, Cancer Treat. Rev. 23, 209–240 (1997).PubMedCrossRefGoogle Scholar
  51. 51.
    H. Mizutani, S. Tada-Oikawa, Y. Hiraku, M. Kojima and S. Kawanishi, Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide, Life Sci. 76, 1439–1453 (2005).PubMedCrossRefGoogle Scholar
  52. 52.
    P. M’Bemba-Meka, N. Lemieux and S.K. Chakrabarti, Role of oxidative stress and intracellular calcium in nickel carbonate hydroxide-induced sister-chromatid exchange, and alterations in replication index and mitotic index in cultured human peripheral blood lymphocytes, Arch. Toxicol. 81, 89–99 (2007).PubMedCrossRefGoogle Scholar
  53. 53.
    R.J. Preston, J.R. San Sebastian and A.F. McFee, The in vitro human lymphocyte assay for assessing the clastogenicity of chemical agents, Mutat. Res. 189, 175–183 (1987).PubMedCrossRefGoogle Scholar
  54. 54.
    P.D.L. Lima, D.S. Leite, M.C. Vasconcellos, B.C. Cavalcanti, R.A. Santos, L.V. Costa-Lotufo, C. Pessoa, M.O. Moraes and R.R. Burbano, Genotoxic effects of aluminum chloride in cultured human lymphocytes treated in different phases of cell cycle, Food Chem. Toxicol. 45, 1154–1159 (2007).PubMedCrossRefGoogle Scholar
  55. 55.
    C.X. Zhang and S.J. Lippard, New metal complexes as potential therapeutics, Curr. Opin. Chem. Biol. 7, 481–489 (2003).PubMedCrossRefGoogle Scholar
  56. 56.
    J. Kasparkova, O. Novakova, V. Marini, Y. Najajreh, D. Gibson, J.-M. Perez and V. Brabec, Activation of trans geometry in bifunctional mononuclear platinum complexes by a piperidine ligand. Mechanistic studies on antitumor action, J. Biol. Chem. 278, 47516–47525 (2003).PubMedCrossRefGoogle Scholar
  57. 57.
    V. Brabec and J. Kasparkova, Modifications of DNA by platinum complexes. Relation to resistance of tumors to platinum antitumor drugs, Drug Resist. Updat. 8, 131–146 (2005).PubMedCrossRefGoogle Scholar
  58. 58.
    D. Anderson, J.B. Bishop, R.C. Garner, P. Ostrosky-Wegman and P.B. Selby, Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks, Mutat. Res. 330, 115–181 (1995).PubMedGoogle Scholar
  59. 59.
    P. Sánchez-Suárez, P. Ostrosky-Wegman, F. Gallegos-Hernández, R. Peñarroja-Flores, J. Toledo-García, J.L. Bravo, E.R. del Castillo and L. Benítez-Bribiesca, DNA damage in peripheral blood lymphocytes in patients during combined chemotherapy for breast cancer, Mutat. Res. 640, 8–15 (2008).PubMedGoogle Scholar
  60. 60.
    E. Rojas, R. Montero, L.A. Herrera, M. Sordo, M.E. Gonsebatt, R. Rodriguez and P. Ostrosky-Wegman, Are mitotic index and lymphocyte proliferation kinetics reproducible endpoints in genetic toxicology testing? Mutat. Res. 282, 283–286 (1992).PubMedCrossRefGoogle Scholar
  61. 61.
    A. Dhawan, M.A. Kayani, J.M. Parry, E. Parry and D. Anderson, Aneugenic and clastogenic effects of doxorubicin in human lymphocytes, Mutagenesis 18, 487–490 (2003).PubMedCrossRefGoogle Scholar
  62. 62.
    A. Fucic, A. Jazbec, A. Mijic, D. Seso-Simic and R. Tomek, Cytogenetic consequences after occupational exposure to antineoplastic drugs, Mutat. Res. 416, 59–66 (1998).PubMedGoogle Scholar
  63. 63.
    S.W. Maluf and B. Erdtmann, Follow-up study of the genetic damage in lymphocytes of pharmacists and nurses handling antineoplastic drugs evaluated by cytokinesis-block micronuclei analysis and single cell gel electrophoresis assay, Mutat. Res. 471, 21–27 (2000).PubMedGoogle Scholar
  64. 64.
    C.S. Djuzenova, D. Schindler, H. Stopper, H. Hoehn, M. Flentje and U. Oppitz, Identification of ataxia telangiectasia heterozygotes, a cancer-prone population, using the single-cell gel electrophoresis (Comet) assay, Lab. Invest. 79, 699–705 (1999).PubMedGoogle Scholar
  65. 65.
    X. Lin, C.G. Wood, L. Shao, M. Huang, H. Yang, C.P. Dinney and X. Wu, Risk assessment of renal cell carcinoma using alkaline comet assay, Cancer 110, 282–288 (2007).PubMedCrossRefGoogle Scholar
  66. 66.
    M.B. Schabath, M.R. Spitz, H.B. Grossman, K. Zhang, C.P. Dinney, P.J. Zheng and X. Wu, Genetic instability in bladder cancer assessed by the comet assay, J Natl Cancer Inst. 95, 540–547 (2003).PubMedCrossRefGoogle Scholar
  67. 67.
    L. Shao, J. Lin, M. Huang, J.A. Ajani and X. Wu, Predictors of esophageal cancer risk: assessment of susceptibility to DNA damage using comet assay, Genes, Chromosomes Cancer 44, 415–422 (2005).PubMedCrossRefGoogle Scholar
  68. 68.
    I. Witte, U. Plappert, H. de Wall and A. Hartmann, Genetic toxicity assessment: employing the best science for human safety evaluation part III: the comet assay as an alternative to in vitro clastogenicity tests for early drug candidate selection, Toxicol Sci. 97, 21–26 (2007).PubMedCrossRefGoogle Scholar
  69. 69.
    A.R. Trzeciak, J. Kowalik, E. Małecka-Panas, J. Drzewoski, M. Wojewodzka, T. Iwanenko and J. Błasiak, Genotoxicity of chromium in human gastric mucosa cells and peripheral blood lymphocytes evaluated by the single cell gel electrophoresis (comet assay), Med. Sci. Monit. 6, 24–29 (2000).PubMedGoogle Scholar
  70. 70.
    K. Sekihashi, A. Yamamoto, Y. Matsumura, S. Ueno, M. Watanabe-Akanuma, F. Kassie, S. Knasmüller, S. Tsuda and Y.F. Sasaki, Comparative investigation of multiple organs of mice and rats in the comet assay, Mutat. Res. 517, 53–75 (2002).PubMedGoogle Scholar
  71. 71.
    J.P. Banath, M. Fushiki and P.L. Olive, Rejoining of DNA single- and double-strand breaks in human white blood cells exposed to ionizing radiation, Int. J. Radiat. Biol. 7, 649–660 (1998).Google Scholar
  72. 72.
    M. Dusinská, A. Collins, A. Kazimírová, M. Barancoková, V. Harrington, K. Volkovová, M. Staruchová, A. Horská, L. Wsólová, A. Kocan, J. Petrík, M. Machata, B. Ratcliffe and S. Kyrtopoulos, Genotoxic effects of asbestos in humans, Mutat. Res. 553, 91–102 (2004).PubMedGoogle Scholar
  73. 73.
    A. Alapetite, A. Benoit, E. Moustacchi and A. Sarasin, The comet assay as a repair test for prenatal diagnosis of xeroderma pigmentosum and trichothiodystrophy, J. Invest. Dermatol. 108, 154–159 (1997).PubMedCrossRefGoogle Scholar
  74. 74.
    J.S. Bertram, The molecular biology of cancer, Mol. Aspects Med. 21, 167–223 (2001).CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Alessandra de Santana Braga Barbosa Ribeiro
    • 1
  • Cláudio Carlos da Silva
    • 2
    • 3
  • Flávia de Castro Pereira
    • 1
  • Aliny Pereira de Lima
    • 1
  • Cesar Augusto Sam Tiago Vilanova-Costa
    • 1
  • Simone Santos Aguiar
    • 1
  • Luiz Alfredo Pavanin
    • 4
  • Aparecido Divino da Cruz
    • 2
    • 3
  • Elisângela de Paula Silveira-Lacerda
    • 1
  1. 1.Laboratório de Genética Molecular e Citogenética, Instituto de Ciências BiológicasUniversidade Federal de Goiás-UFGGoiâniaBrazil
  2. 2.Núcleo de Pesquisas Replicon, Departamento de BiologiaUniversidade Católica de Goiás-UCGGoiâniaBrazil
  3. 3.LaGene-Laboratório de Citogenética Humana e Genética MolecularSecretaria de Saúde do Estado de Goiás-SES-GOGoiâniaBrazil
  4. 4.Instituto de QuímicaUniversidade Federal de Uberlândia-UFUUberlândiaBrazil

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