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Genetic Effects Induced by Nickel Sulfate in Germline and Somatic Cells of WR Mice

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Abstract

We examined the effects of nickel sulfate at doses 0.5 to 5.0 mg/kg (1/200–1/20 LD50) on the frequency of dominant lethal mutations and double-strand DNA breaks (DSBs) in germline cells and on an increase in frequency in gene mutations W y in pigment cells of first-generation mice. The results indicated that spermatogenesis stages most sensitive to nickel sulfate (at a dose of 1.0 mg/kg) are spermatozoids, early spermatids, late spermatocytes, and stem spermatogonia. No statistically significant increase in the total TSB level was detected in spermatozoids 4 weeks after exposure. At the same time, a significant (P < 0.05) increase in percentage of cells with an extremely high level of DNA fragmentation (supposedly apoptotic cells) was observed upon exposure at a dose of 0.5 mg/kg. Nickel sulfate at doses of 5.0 and 1.0 mg/kg induced a marked increase in the c-kit gene expression in pigment cells of heterozygous first-generation WR mice as compared to control (P < 0.001). It was shown that the nonobservable adverse effect level (NOAEL) of nickel sulfate on the dominant lethal mutation frequency and gene mutations was 1/200 LD50, while the lowest observable adverse effect level (LOAEL) was 1/100 LD50.

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REFERENCES

  1. Chashin, V.P., Artunina, G.P., and Nortseth, T., Congenital Defects, Abortion and Other Health Effects in Nickel Refinery Workers, Sci. Total Environ., 1994, vol. 148, pp. 257–291.

    Google Scholar 

  2. Toxicological Profile for Nickel (Update), US Department of Health & Human Services Public Health Service, Agency for Toxic Substances and Diases Registry, 1997, pp. 51–52, 82, 124–129.

  3. Klein, C.B., Kargasin, B., and Su, L., Metal Mutagenic Chinese Hamster Cell Lines, Environ. Health Perspect., 1994, vol. 102,suppl. 3, pp. 63–67.

    Google Scholar 

  4. Miki, H., Kasprzak, K.S., Kenney, S., and Heine, U.I., Inhibition of Intercellular Communication by Nickel (II): Antagonistic Effect of Magnesium, Carcinogenesis, 1987, vol. 8, pp. 1757–1760.

    PubMed  Google Scholar 

  5. Sobti, R.C. and Gill, R.K., Incidence of Micronuclei and Abnormalities in the Head of Spermatozoa Caused by Salts of a Heavy Metal Nickel, Cytologia, 1988, vol. 54, pp. 249–254.

    Google Scholar 

  6. Dhir, H., Agarwal, K., Sharma, A., et al., Modifying Role of Phyllanthes emlica and Ascorbic Acid against Nickel Clastogenicity in Mice, Cancer Lett., 1991, vol. 59, pp. 9–18.

    Article  PubMed  Google Scholar 

  7. Andersen, O., Effects of Coal Combustion Products and Metal Compounds on Sister Chromatid Exchange (SCE) in a Macrophage Cell Line, Environ. Health Perspect., 1983, vol. 47, pp. 239–253.

    PubMed  Google Scholar 

  8. Arrouijal, F.Z., Marsin, D., Hildebrand, H.F., et al., Differences in Genotoxic Activity of α-Ni3S2 on Human Lymphocytes from Nickel-Hypersentized and Nickel-Unsensitized Donors, Mutagenesis, 1992, vol. 7, no.3, pp. 183–187.

    PubMed  Google Scholar 

  9. Saxholm, H.J.K., Reith, A., and Brogger, A., Oncogenic Transformation and Cell Increased Sister Chromatid Exchange in Human Lymphocytes by Nickel Subsulfide, Cancer Res., 1981, vol. 41, pp. 4136–4139.

    PubMed  Google Scholar 

  10. Wulf, H.C., Sister Chromatid Exchanges in Human Lymphocytes Exposed to Nickel and Lead, Dan. Med. Bull., 1980, vol. 27, pp. 40–42.

    PubMed  Google Scholar 

  11. Sahu, R.K., Katsifis, S.P., Kinney, P.L., and Christie, N.T., Effect of Nickel Sulfate, Lead Sulfate, and Sodium Arsenite Alone and with UV Light on Cultured Human Lymphocytes, J. Mol. Toxicol., 1989, vol. 2, pp. 129–136.

    Google Scholar 

  12. Deknudt, G.H. and Leonard, A., Mutagenicity Tests with Nickel Salts in the Male Mouse, Toxicology, 1982, vol. 25, pp. 289–292.

    Article  PubMed  Google Scholar 

  13. Jacquet, P. and Mayence, A., Application of the In Vitro Embryo Culture to the Study of the Mutagenic Effects of Nickel in Male Germ Cells, Toxicol. Lett., 1982, vol. 11, pp. 193–197.

    Article  PubMed  Google Scholar 

  14. Patierno, S.R., Sugiyama, M., Basilion, J.P., and Costa, M., Preferential DNA-Protein Crosslinking by NiCl2 in Magnesium-Insoluble Regions of Fractionated Chinese Hamster Ovary Cell Chromatin, Cancer. Res., 1985, vol. 45, pp. 5787–5794.

    PubMed  Google Scholar 

  15. Kasprzak, K.S., The Role of Oxidative Damage in Metal Carcinogenicity, Chem. Res. Toxicol., 1991, vol. 4, pp. 604–615.

    Article  PubMed  Google Scholar 

  16. Hartwig, A., Mullenders, L.H.F., Schlepegrell, R., et al., Nickel(II) Interferes with the Incision Step in Nucleotide Excision Repair in Mammalian Cells, Cancer. Res., 1994, vol. 54, pp. 4045–4051.

    PubMed  Google Scholar 

  17. Lei, Y.X., Chen, J.K., and Wu, Z.L., Detection of DNA Strand Breaks, DNA-Protein Crosslinks, and Telomerase Activity in Nickel-Transformed BALB/c 3T3 Cells, Teratogen. Carcinogen. Mutagen., 2001, vol. 21, no.6, pp. 463–471.

    Google Scholar 

  18. Elakov, A.L., Mironova, J.V., Osipov, A.N., and Sypin, V.D., Comparative Study of Nickel and Cadmium Influence on Spleen Lymphocytes of Different Age Mice, Environment and Human Health: The Complete Works of International Ecologic Forum, June 29–July 2, 2003, St. Petersburg, Russia, Sofronov, G.A., Ed., St. Petersburg: SpecLit, 2003, p. 577.

    Google Scholar 

  19. Mastromatteo, E., Jant Memorial Lecture: Nickel, Am. Ind. Hyg. Assoc. J., 1986, vol. 47, pp. 589–601.

    PubMed  Google Scholar 

  20. Blandova, Z.K., Dushkin, V.A., Malashenko, A.M., et al., Linii laboratornykh myshei dlya mediko-biologicheskikh issledovanii (Laboratory Strains of Mice for Medical-Biological Investigations), Moscow: Nauka, 1983, 199 p.

    Google Scholar 

  21. Malashenko, A.M. and Surkova, N.I., WR, A New Mouse Line Highly Sensitive to the Cytogenetic Effect of ThioTEP, Tsitol. Genet., 1979, vol. 13, pp. 387–391.

    PubMed  Google Scholar 

  22. Yang-Feng, T.L., Ulrich, A., and Franke, A., The Oncogene c-kit (KIT) Is Located on Man Chromosome 4 and Mouse Chromosome 5, Cytogenet. Cell Genet., 1987, vol. 46, p. 723.

    Google Scholar 

  23. Shevchenko, V.A and Pomerantseva, M.D., Dominant Lethal Mutations, in Geneticheskie posledstviya ioniziruyushchikh izluchenii (Genetic Consequences of Ionizing Radiation), Moscow: Nauka, 1985, pp. 41–42.

    Google Scholar 

  24. Ehling, U.H., Machemer, L., Buselmaier, W., et al., Standard Protocol for the Dominant Lethal Test on Male Mice, Arch. Toxicol., 1978, vol. 39, pp. 173–185.

    Article  Google Scholar 

  25. Fahrig, R., A Mammalian Spot-Test: Induction of Genetic Alterations in Pigment Cells of Mouse Embryos with X-Rays and Chemical Mutagens, Mol. Gen. Genet., 1975, vol. 138, no.4, pp. 309–314.

    Article  PubMed  Google Scholar 

  26. Singh, N.P. and Stephens, R.E., X-Ray-Induced DNA Double-Strand Breaks in Human Sperm, Mutagenesis, 1998, vol. 13, no.1, pp. 75–79.

    PubMed  Google Scholar 

  27. Collins, A.R., Ma, A.G., and Duthie, S.J., The Kinetics of Repair of Oxidative DNA Damage (Strand Breaks and Oxidized Pyrimidine Dimers in Human Cells), Mutat. Res., 1995, vol. 336, no.1, pp. 69–77.

    PubMed  Google Scholar 

  28. Domshlak, M.G., Chirkova, E.M., and Strekalova, E.E., Mutagenic Effect of Ethylenimine (EI) on Mouse Gametes upon Inhalation or Introduction into the Stomach, Laboratornye zhivotnye v meditsinskikh issledovaniyakh (Laboratory Animals in Medical Studies, Moscow: Nauch.-Issled. Lab. Eksp. Biol. Modelei, 1974, pp. 42–44.

    Google Scholar 

  29. Domshlak, M.G., Genetic Effect of Low Doses of Industrial Chemicals, in Meditsina truda na predpriyatiyakh g. Moskvy (Occupational Medicine at Moscow Enterprises), Moscow: Inst. Med. Truda, 1998, pp. 148–150.

    Google Scholar 

  30. Fomenko, V.N., Domchlak, M.G., Katosova, L.D., et al., Mutagenic and Gonadotropic Effects of Styrene, Proc. of the Finish-Soviet Joint Symp. on Industrial Hygiene and Toxicology, Helsinki, 1984, pp. 48–57.

  31. Fomenko, V.N., Domchlak, M.G., Katosova, L.D., et al., General Toxic and Specific Chrome Effect, Proc. 6th Finish-Soviet Joint Symp. on Occupational Health, Rovaniemi, 1987, pp. 26–31.

  32. Genroso, W.M., Russel, L.B., Huff, S.W., et al., Effect of Dose on the Induction of Dominant Lethal Mutations and Heritable Translocations with Methyl Methanesulfonate in Male Mice, Genetics, 1974, vol. 77, pp. 741–752.

    PubMed  Google Scholar 

  33. Bateman, A.J., Mutagenic Sensitivity of Maturing Germ Cells in the Male Mouse, Heredity, 1958, vol. 12, pp. 213–232.

    Google Scholar 

  34. Ehling, U.H., Differential Spermatogenic Response of Mice to the Induction of Mutations by Antineoplastic Drugs, Iutat. Res., 1974, vol. 26, pp. 285–295.

    Google Scholar 

  35. Ehling, U.H. and Neuhauser-Klaus, A., Induction of Specific-Locus and Dominant Lethal Mutations in Male Mice by in N-Propyl and Isopropyl Methanesulfonate, Mutat. Res., 1995, vol. 328, pp. 73–82.

    PubMed  Google Scholar 

  36. Burlakova, E.B., Distant Consequences of the Integral Effect of Low Doses and Damaging Environmental Factors on Population Viability, in Budushchee natsii (Future of the Nation), Moscow, 1995, part 2, pp. 64–76.

  37. Svendsgaard, D. and Calabrase, E.J., U-Shaped Dose Response Relationships in Toxicology, XXI Medichen Congr., 18–21 October, 1994, Melbourne, 1994, pp. 106–124.

  38. Sakkas, D., Mariethoz, E., Manicardi, G., et al., Origin of DNA Damage in Ejaculated Human Spermatozoa, Rev. Reprod., 1999, vol. 4, pp. 31–37.

    Article  PubMed  Google Scholar 

  39. McPherson, S.M.G. and Longo, F.J., Localization of DNase I-Hypersensitive Regions during Rat Spermatogenesis: Stage-Dependent Patterns and Unique Sensitivity of Elongating Spermatids, Mol. Reprod. Dev., 1992, vol. 31, pp. 268–279.

    Article  PubMed  Google Scholar 

  40. McPherson, S.M.G. and Longo, F.J., Nicking of Rat Spermatid and Spermatozoa DNA: Possible Involvement of DNA Topoisomerase II, Dev. Biol., 1993, vol. 158, pp. 122–130.

    Article  PubMed  Google Scholar 

  41. McPherson, S.M.G. and Longo, F.J., Chromatin Structure-Function Alterations during Mammalian Spermatogenesis: DNA Nicking and Repair in Elongating Spermatids, Eur. J. Histochem., 1993, vol. 37, pp. 109–128.

    PubMed  Google Scholar 

  42. Sakkas, D., Manicardi, G.C., Bianchi, P.G., et al., Relationship between the Presence of Endogenous Nicks and Sperm Chromatin Packaging in Maturing and Fertilizing Mouse Spermatozoa, Biol. Reprod., 1995, vol. 52, pp. 1149–1155.

    PubMed  Google Scholar 

  43. Suda, T., Takahashi, T., Golstein, P., and Nagata, S., Molecular Cloning and Expression of the Fas Ligand, a Novel Member of the Tumor Necrosis Factor Family, Cell (Cambridge, Mass.), 1993, vol. 75, pp. 1169–1178.

    Article  PubMed  Google Scholar 

  44. Lee, J., Richburg, J.H., Younkin, S.C., and Boekelheide, K., The Fas System Is a Key Regulator of Germ Cell Apoptosis in the Testis, Endocrinology, 1997, vol. 138, pp. 2081–2088.

    Article  PubMed  Google Scholar 

  45. Domshlak, M.G., Quantitation of Genetic Risk and Relative Genetic Efficiency for Some Alkylating Agents, Zh. Med. Trula Prom. Ekol., 2003, no. 9, pp. 33–39.

  46. Domshlak, M.G., Chirkova, E.M., Malashenko, A.M., et al., Registration of Changes in the W y Gene in Somatic Mouse Cells As a Means to Estimate the Genetic Effect in Toxicological Studies, Gig. Tr. Prof. Zabol., 1981, no. 7, pp. 52–53.

  47. Shustov, V.Ya., Mikroelementy v gematologii (Microelements in Hematology), Moscow: Meditsina, 1967.

    Google Scholar 

  48. Jasim, S. and Tjalve, H., Effect of Sodium Pyridimethione on the Uptake and Distribution of Nickel, Cadmium and Zinc in Pregnant and Non-Pregnant, Toxicology, 1986, vol. 38, pp. 327–350.

    Article  PubMed  Google Scholar 

  49. Leonard, A., Gerber, G.B., and Jacouet, P., Carcinogenicity, Mutagenicity and Teratogenisity of Nickel, Mutat. Res., 1981, vol. 87, pp. 1–15.

    PubMed  Google Scholar 

  50. Ehling, U.H., Evaluation of Genetic Hazards in Man from Radiation and Chemical Mutagens, Radiobiological Equivalents of Chemical Pollutants, International Atomic Energy, 1980, pp. 71–81.

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Translated from Genetika, Vol. 41, No. 7, 2005, pp. 894–901.

Original Russian Text Copyright © 2005 by Domshlak, Elakov, Osipov.

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Domshlak, M.G., Elakov, A.L. & Osipov, A.N. Genetic Effects Induced by Nickel Sulfate in Germline and Somatic Cells of WR Mice. Russ J Genet 41, 728–734 (2005). https://doi.org/10.1007/s11177-005-0152-3

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