Pathways in the Chromium(VI)-Mediated Formation of DNA Lesions: A Review

  • A. Kortenkamp
  • M. Casadevall
  • P. Da Cruz Fresco
  • R. O. J. Shayer
Part of the NATO ASI Series book series (ASEN2, volume 26)


The advent of mutation assays, the development of sensitive methods for the analysis of DNA damage, and the application of spectroscopic methods to biomedical problems have greatly aided our understanding of the mechanisms by which chromium(VI) compounds exert their carcinogenicity. It is now well established that chromium(VI) compounds are strong mutagens, causing point mutations, chromosome aberrations and sister-chromatid exchanges in microorganisms, cultured mammalian cells and laboratory animals [1]. A number of DNA lesions including single strand breaks, alkali-labile sites, DNA-protein cross links, DNA- interstrand cross links [2–11], and recently DNA-amino acid cross links [12] have been observed after treatment of cultured mammalian cells with chromium(VI). The finding that chromium(VI) itself is unreactive towards DNA [13, 14] has prompted research into the reductive conversion of chromium(VI), ultimately to chromium(III), as a crucial step in the formation of DNA lesions.


Strand Break Cross Link Single Strand Break Abasic Site Interstrand Cross Link 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    IARC (1990) Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, vol 49, Chromium. Nickel and Welding, International Agency on the Research of Cancer, Lyon.Google Scholar
  2. 2.
    Whiting, R.F., Stich, H.F., and Koropatnik, D.J. (1979) DNA damage and DNA repair in cultured human cells exposed to chromate, Chem. Biol. Interact 26, 267–280.CrossRefGoogle Scholar
  3. 3.
    Douglas, G.R., Bell, R.D., Grant, C.E., Wytsma, D and Bora, K.C. (1980) Effect of lead chromate on chromosome aberration, sister-chromatid exchange and DNA damage in mammalian cells in vitro, Mutat Res. 77, 157–163.CrossRefGoogle Scholar
  4. 4.
    Tsapakos, M.J., Hampton, T.H., and Jennette, K.E. (1981) The carcinogen chromate induces DNA-crosslinks in rat liver and kidney, J. Biol. Chem. 256, 3623–3626.Google Scholar
  5. 5.
    Tsapakos, M.J., Hampton, T.H., and Wetterhahn, K.E. (1983) Chromium(VI)-induced DNA lesions and chromium distribution in rat kidney, liver, and lung, Cancer Res. 43, 5662–5667.Google Scholar
  6. 6.
    Wedrychowski, A., Schmidt, W.N., Ward, W.S., and Hmlica, L. (1985) Chromium-induced cross-linking of nuclear proteins and DNA, J Biol. Chem. 260, 7150–7155.Google Scholar
  7. 7.
    Christie, N., Cantoni, O., Evans, R.M., Meyn, R.E., and Costa, M. (1984) Use of mammalian DNA repair-deficient mutants to assess the effects of toxic metal compounds on DNA, Biochem. Pharmacol. 33, 1661–1670.CrossRefGoogle Scholar
  8. 8.
    Cantoni, O. and Costa, M. (1984) Analysis of the induction of alkali sensitive sites in the DNA by chromate and other agents that induce single strand breaks, Carcinogenesis 5, 1207–1209.CrossRefGoogle Scholar
  9. 9.
    Sugiyama, M., Wang, X.W., and Costa, M. (1986) Comparison of DNA lesions and cytotoxicity induced by calcium chromate in human, mouse, and hamster cell lines, Cancer Res. 46, 4547–4551.Google Scholar
  10. 10.
    Sugiyama, M., Patierno, S.R., Cantoni, O., and Costa, M. (1986) Characterization of DNA lesions induced by calcium chromate in synchronous and asynchronous cultured mammalian cells, Mol. Pharmacol. 29, 606–613.Google Scholar
  11. 11.
    Hamilton, J.W. and Wetterhahn, K.E. (1986) Chrorrnum(VI)-induced DNA damage in chick embryo liver and blood cells in vivo, Carcinogenesis 7, 2085–2088.CrossRefGoogle Scholar
  12. 12.
    Zhitkovich, A., Voitkun, V., and Costa, M. (1995) Glutathione and free amino acids form stable complexes with DNA following exposure of intact mammalian cells to chromate, Carcinogenesis 16, 907–913.CrossRefGoogle Scholar
  13. 13.
    Jennette, K.E. (1979) Chromate metabolism in liver microsomes, Biol. Trace Elem. Res. 1, 55–62CrossRefGoogle Scholar
  14. 14.
    Tsapakos, M.J. and Wetterhahn, K.E. (1983) Interaction of chromium with nucleic acids, Chem. Biol. Interact. 46, 265–277CrossRefGoogle Scholar
  15. 15.
    Ryberg, D., and Alexander, J. (1984) Inhibitory action of hexavalent chromium on the mitochondnal respiration and a possible coupling to the reduction of chromium(VI), Biochem Pharmacol. 33, 2461–2466.CrossRefGoogle Scholar
  16. 16.
    Connett, P. and Wetterhahn, K.E. (1983) Metabolism of the carcinogen chromate by cellular constituents. Struct. Bonding 54, 93–124.CrossRefGoogle Scholar
  17. 17.
    Wetterhahn-Jennette, K.E. (1982) Microsomal reduction of the carcinogen chromate produces chromium(V), J. Amer Chem. Soc 104, 874.Google Scholar
  18. 18.
    O’Bnen, P., Barrett, J., and Swanson, F. (1985) Chromium(V) can be generated in the reduction of chromium(VI) by glutathione, Inorg. Chim. Acta 108, L19.CrossRefGoogle Scholar
  19. 19.
    Cupo, D.Y. and Wetterhahn, K.E. (1984) Repair of chromate-induced DNA damage in chick embryo hepatocytes, Carcinogenesis 5, 1705–1708.CrossRefGoogle Scholar
  20. 20.
    Robison, S.H., Cantoni, O., and Costa, M. (1984) Analysis of metal-induced DNA lesions and DNA repair replication in mammalian cells, Mutat. Res. 131, 173–181.CrossRefGoogle Scholar
  21. 21.
    Snyder, R.D. (1988) Role of active oxygen in metal-induced DNA strand breakage in human diploid fibroblasts, Mutat. Res. 193, 237–246.CrossRefGoogle Scholar
  22. 22.
    Miller III, C.A. and Costa, M. (1988) Characterization of DNA-protein complexes induced in intact cells by the carcinogen chromate, Mol Carcinogenesis 1, 125–133.CrossRefGoogle Scholar
  23. 23.
    Miller III, C. A. and Costa, M. (1989) Immunological detection of DNA-protein complexes induced by chromate, Carcinogenesis 10, 667–672.CrossRefGoogle Scholar
  24. 24.
    Costa, M. (1991) DNA-protein complexes induced by chromate and other carcinogens, Env Health Perspect. 92, 45–52CrossRefGoogle Scholar
  25. 25.
    Standeven, A.M., and Wetterhahn, K.E. (1991) Is there a role for reactive oxygen species in the mechanism of chromium(VI) carcinogenesis?, Chem. Res. Toxicol. 4, 616–625.CrossRefGoogle Scholar
  26. 26.
    Cupo, D.Y. and Wetterhahn, K.E. (1985) Modification of chronuum(VI)-induced DNA damage by glutathione and cytochromes P 450 in chicken embryo hepatocytes, Proc. Natl. Acad. Sci. 82, 6755–6759.CrossRefGoogle Scholar
  27. 27.
    Misra, M, Alcedo, J.A., and Wetterhahn, K.E. (1994) Two pathways for chromium(VI)-induced DNA damage in 14 day chick embryos: Cr-DNA binding in liver and 8-oxo-2’-deoxyguanosine in red blood cells, Carcinogenesis 15, 2911–2917.CrossRefGoogle Scholar
  28. 28.
    Buttner, B. and Beyersmann, D. (1985) Modification of the erythrocyte anion carrier by chromate, Xenobiotica 15, 735–741.CrossRefGoogle Scholar
  29. 29.
    Kortenkamp, A., O’Brien, P., and Beyersmann, D. (1987) Uptake of chromium(III) complexes by erythrocytes, Toxicol. Environ. Chem. 14, 23–32.CrossRefGoogle Scholar
  30. 30.
    Sehlmeyer, U., Hechtenberg, S., KJyszcz, H., and Beyersmann, D. (1990) Accumulation of chromium in Chinese hamster V79 cells and nuclei, Arch. Toxicol. 64, 506–508.CrossRefGoogle Scholar
  31. 31.
    Connett, P. and Wetterhahn, K.E. (1985) In vitro reaction of the carcinogen chromate with cellular thiols and carboxylic acids, J. Amer. Chem. Soc. 107, 4282–4288.CrossRefGoogle Scholar
  32. 32.
    Suzuki, Y. (1988) Reduction of hexavalent chromium by ascorbic acid in rat lung lavage fluid, Arch. Toxicol. 62, 116–122.CrossRefGoogle Scholar
  33. 33.
    Suzuki, Y. (1990) Synergism of ascorbic acid and glutathione in the reduction of hexavalent chromium in vitro, Ind. Health 28, 9–19.CrossRefGoogle Scholar
  34. 34.
    Suzuki, Y., and Fukuda, K. (1990) Reduction of hexavalent chromium by ascorbic acid and glutathione with special reference to the rat lung, Arch. Toxicol. 64, 169–176.CrossRefGoogle Scholar
  35. 35.
    Standeven, A.M., and Wetterhahn, K.E. (1991) Ascorbate is the principal reductant of chromium(VI) in rat liver and kidney ultrafiltrates, Carcinogenesis 12, 1733–1737.CrossRefGoogle Scholar
  36. 36.
    Standeven, A.M., and Wetterhahn, K.E. (1992) Ascorbate is the principal reductant iof chromium(VI) in rat lung ultrafiltrates and cytosols, and mediates chromium-DNA binding in vitro, Carcinogenesis 13, 1319–1324.CrossRefGoogle Scholar
  37. 37.
    Mikalsen, A., Alexander, J., Ryberg, D. (1989) Microsomal metabolism of hexavalent chromium:Inhibitory effect of oxygen and involvement of cytochrome P 450, Chem.-Biol. Interact. 69, 175–192.CrossRefGoogle Scholar
  38. 38.
    Mikalsen, A., Alexander, J., Wallin, J., Ingelmann-Sundberg, M., and Andersen, R.A. (1991) Reductive metabolism and protein binding of chromium(VI) by P450 protein enzymes, Carcinogenesis 12, 825–831.CrossRefGoogle Scholar
  39. 39.
    Kawanishi, S., Inoue, S., and Sano, S. (1986) Mechanisms of DNA cleavage induced by sodium chromate(VI) in the presence of hydrogen peroxide, J. Biol. Chem. 261, 5952–5958.Google Scholar
  40. 40.
    Shi, X. and Dalai, N. (1990) On the hydroxyl radical formation in the reaction between hydrogen peroxide and biologically generated chromium(V) species, Arch. Biochem. Biophys. 111, 342–350.CrossRefGoogle Scholar
  41. 41.
    Tomaszewski, K.E., Agarwal, D.K., and Melnick, R.L. (1986) In vitro steady-state levels of hydrogen peroxide after exposure of male F344 rats and female B6C3F1 mice to hepatic peroxisome proliferators, Carcinogenesis 7, 1871–1876.CrossRefGoogle Scholar
  42. 42.
    Sugiyama, M., Ando, A., Furuno, A., Burr Furlong, N., Hidaka, T., and Ogura, R. (1987) Effects of vitamin E, vitamin B2, and selenite on DNA single strand breaks induced by sodium chromate (VI), Cancer Lett. 38, 1–7.CrossRefGoogle Scholar
  43. 43.
    Sugiyama, M., Tsuzuki, K., and Ogura, R. (1991) Effect of ascorbic acid on DNA damage, cytotoxicity, glutathione reductase, and formation of paramagnetic chromium in chines hamster V-79 cell treated with sodium chromate(VI), J. Biol. Chem. 266, 3383–3386.Google Scholar
  44. 44.
    Capellmann, M., Mikalsen, A., Hindrun, M., and Alexander, J. (1995) Influence of reducing compounds on the formation of DNA-protein cross links in HL-60 cells induced by hexavalent chromium, Carcinogenesis 16, 1135–1139.CrossRefGoogle Scholar
  45. 45.
    Sugiyama, M., Ando, A., Nakao, K., Ueta, H., Hidaka, T., and Ogura, R. (1989) Influence of vitamin B2 on formation of chromium(V), alkali-labile sites, and lethality of sodium chromate(VI) in Chinese hamster V-79 cells, Cancer Res. 49, 6180–6184.Google Scholar
  46. 46.
    Sugiyama, M., Ando, A., and Ogura, R. (1989) Vitamin B2-enhancement of sodium chromate(VI)-induced DNA single strand breaks: ESR study of the action of vitamin B2, Biochem. Biophys. Res. Comm. 159, 1080–1085.CrossRefGoogle Scholar
  47. 47.
    Sugiyama, M., Ando, A, and Ogura, R. (1989) Effect of vitamin E on survival, glutathione reductase and formation of chromium(V) in Chines hamster V-79 cells treated with sodium chromate(VI), Carcinogenesis 10, 737–741.CrossRefGoogle Scholar
  48. 48.
    Sugiyama, M. (1989) Effects of vitamin E and vitamin B2 on chromate-induced DNA lesions, Biol. Trace Elem. Res. 21, 399–404.CrossRefGoogle Scholar
  49. 49.
    Sugiyama, M. (1991) Effects of vitamins on chromium(VI)-induced DNA damage, Environ Health Perspect 92, 63–70.CrossRefGoogle Scholar
  50. 50.
    Sugiyama, M, Lin, X., and Costa, M. (1991) Protective effect of vitamin E against chromosomal aberrations and mutations induced by sodium chromate in Chinese hamster V-79 cells, Mutat. Res. 260, 19–23.CrossRefGoogle Scholar
  51. 51.
    Sugiyama, M. (1992), Role of physiological antioxidants in chromium(VI)-induced cellular injury, Free Radical Biol. Med. 112, 397–407.CrossRefGoogle Scholar
  52. 52.
    Sugden, K.D., Burns, R.B., and Rodgers, S.J. (1990) An oxygen dependence in chromium mutagenesis, Mutat. Res. 244, 239–244.CrossRefGoogle Scholar
  53. 53.
    Yang, J.L., Hsieh, Y.C., Wu, C.W., and Lee, T.C. (1992) Mutational specificity of chromium(VI) compounds in the hprt locus of Chinese hamster ovary-K1 cells, Carcinogenesis 13, 2053–2057.CrossRefGoogle Scholar
  54. 54.
    Chen, J., and Thilly, W.G. (1994) Mutational spectrum of chromium(VI) in human cells, Mutat. Res. 323, 21–27.CrossRefGoogle Scholar
  55. 55.
    McBride, T.J., Preston, B.D., and Leob, L.A. (1991) Mutagenic spectrum resulting from DNA damage by oxygen radical, Biochemistry 30, 207–213.CrossRefGoogle Scholar
  56. 56.
    Tkeshelashvili, L.K, McBridge, T., Spence, K., and Loeb, L. (1991) Mutation spectrum of copper-induced DNA damage, J. Biol. Chem. 266, 6401–6406.Google Scholar
  57. 57.
    McAuley, A. and Olatunij, M.A. (1977) Metal-ion oxidations in solution. Part XIX. Redox pathways in the oxidation of penicillamine and glutathione by chromium(VI), Can. J. Chem. 55, 335–340Google Scholar
  58. 58.
    O’Brien, P. and Ozolins, Z. (1989) Mechanisms in the reduction of chromium(VI) with glutathione. Inorg Chim. Acta 161, 261–266.CrossRefGoogle Scholar
  59. 59.
    Kortenkamp, A., Casadevall, M, Faux, S., Jenner, A., Shayer, R.O.J., Woodbridge, N., and O’Brien, P. (1996) A role for molecular oxygen in the formation of DNA damage during the reduction of the carcinogen chromium(VI) by glutathione, Arch. Biochem. Biophys. 329, in press.Google Scholar
  60. 60.
    Aiyar, J., Berkovits, H.J., Floyd, R.A., and Werterhahn, K.E. (1991) Reaction of chromium(VI) with glutathione or with hydrogen peroxide, identification of reactive intermediates and their role in chromium(VI) induced DNA damage, Env. Health Perspect 92, 53–92.CrossRefGoogle Scholar
  61. 61.
    O’Brien, P. and Wang, G. (1992) Is a one electron path significant in the reduction of chromate by glutathione under physiological conditions? J. Chem. Soc. Chem. Commun. 690–69Google Scholar
  62. 62.
    O’Brien, P. and Kortenkamp, A. (1994) Chemical models important in understanding the ways in which chromate can damage DNA, Environ. Health Perspect. 102, Suppl.3, 3–10.Google Scholar
  63. 63.
    Wolf, T., Bolt, H.M., and Ottenwälder, H. (1989) Nick translation studies on DNA strand breaks in pBR322 plasmid induced by different chromium species, Toxicol Lett. 47, 295–301CrossRefGoogle Scholar
  64. 64.
    Aiyar, J, Borges, K.M., Floyd, R.A., and Wetterhahn, K.E. (1989) Role of chromium(V), glutathione thiyl radical and hydroxyl radical intermediates in chromium(VI)-induced DNA damage, Toxicol Environ. Chem. 22, 135–148.CrossRefGoogle Scholar
  65. 65.
    Kortenkamp, A., Ozolins, Z., Beyersmann, D, and O’Brien, P. (1989) Generation of PM2 DNA breaks in the course of reduction of chromium(VI) by glutathione, Mutat. Res. 216, 19–26.CrossRefGoogle Scholar
  66. 66.
    Kortenkamp, A., Oetken, G., and Beyersmann, D. (1990) The DNA cleavage induced by a chromium(V) complex and by chromate and glutathione is mediated by activated oxygen species, Mutat. Res. 232, 155–161.CrossRefGoogle Scholar
  67. 67.
    Misra, H.P. (1974) Generation of Superoxide free radical during the autoxidation of thiols, J. Biol. Chem. 249, 2151–2155.Google Scholar
  68. 68.
    Dorfman, L.M. and Adams G.E. (1972) Reactivity of the hydroxyl radical in aqueous solution, US Government Printing Office, Washington DC, NSRDS-NBS46.Google Scholar
  69. 69.
    Goodgame, D.M.L. and Joy, A.M. (1987) EPR study of the Cr(V) and radical species produced in the reduction of Cr(VI) by ascorbate, Inorg. Chim. Acta 135, 115–118.CrossRefGoogle Scholar
  70. 70.
    Steams, D. M. and Wetterhalm, K.E. (1994) Reaction of chromium(VI) with ascorbate produces chromium(V), chromium(IV), and carbon-based radicals, Chem. Res. Toxicol 7, 219–230.CrossRefGoogle Scholar
  71. 71.
    Davies, M.B. (1992) Reactions of L-ascorbic acid with transition metal complexes, Polyhedron 11, 285–321.CrossRefGoogle Scholar
  72. 72.
    Kalus, W.H., Filby, W.G., and Münzner, R. (1982) Chemical aspects of the mutagenic activity of the ascorbic acid autoxidation system, Z. Naturforsch. 37 c, 40–45.Google Scholar
  73. 73.
    Da Cruz Fresco, P. and Kortenkamp, A. (1994) The formation of DNA cleaving species during the reduction of chromate by ascorbate, Carcinogenesis 15, 1773–1778.CrossRefGoogle Scholar
  74. 74.
    Stearns, D.M., Kennedy, L.J., Courtney, K.D., Giangrande, P.H., Phieffer, L.S., and Wetterhahn, K.E. (1995) Reduction of chromium(VI) by ascorbate leads to chromium-DNA binding and DNA strand breaks in vitro, Biochemistry 34, 910–919.CrossRefGoogle Scholar
  75. 75.
    Da Cruz Fresco, P., Shacker, F., and Kortenkamp, A. (1995) The reductive conversion of chromium(VI) by ascorbate gives rise to apurinic/apyrimidinic sites in isolated DNA, Chem. Res. Toxicol. 8, 884–890.CrossRefGoogle Scholar
  76. 76.
    Aiyar, J., Berkovits, H.J., Floyd, R.A., and Wetterhahn, K.E. (1990) Reaction of chromium(VI) with hydrogen peroxide in the presence of glutathione. reactive intermediates and resulting DNA damage, Chem. Res. Toxicol. 3, 595–603.CrossRefGoogle Scholar
  77. 77.
    Shi, X. and Dalai, N. (1990) Evidence for a Fenton-type mechanism for the generation of OH radicals in the reduction of Cr(VI) in cellular media, Arch. Biochem. Biophys. 281, 90–95.CrossRefGoogle Scholar
  78. 78.
    Shi, X., Mao, Y., Knapton, A.D., Ding, M., Rojanasakul, Y., Gannett, P.M., Dalai, N., and Liu, K. (1994) Reaction of Cr(VI) with ascorbate and hydrogen peroxide generates hydroxyl radicals and causes DNA damage; role of a Cr(IV)-mediated Fenton-like reaction, Carcinogenesis 15, 2475–2478.CrossRefGoogle Scholar
  79. 79.
    Shi, X., Dalai, N.S., and Kasprzak, K.S. (1993) Generation of free radicals from hydrogen peroxide and lipid hydroperoxides in the presence of Cr(III), Arch. Biochem. Biophys. 302, 294–299.CrossRefGoogle Scholar
  80. 80.
    Tsou, T.C., Chen, C.L., Liu, T.Y., and Yang, J.L. (1996) Induction of 8-hydroxydeoxyguanosine in DNA by chromium(TII) plus hydrogen peroxide and its prevention by scavengers, Carcinogenesis 17, 103–108.CrossRefGoogle Scholar
  81. 81.
    Casadevall, M. and Kortenkamp, A. (1994) The generation of apurinic/apyrimidinic sites in isolated DNA during the reduction of chromate by glutathione, Carcinogenesis 15, 407–409.CrossRefGoogle Scholar
  82. 82.
    Casadevall, M. and Kortenkamp, A (1995) The formation of both apurinic/apyrimidinic sites and single-strand breaks by chromate and glutathione arises from attack by the same single reactive species and is dependent on molecular oxygen, Carcinogenesis 16, 805–809.CrossRefGoogle Scholar
  83. 83.
    Dedon, P.C. and Goldberg, I.H.(1992) Free-radical mechanisms involved in the formation of sequence-dependent bistranded DNA lesions by the antitumour antibiotics bleomycin, neocarzinostatin, and calicheamicin, Chem. Res. Toxicol. 5, 311–332.CrossRefGoogle Scholar
  84. 84.
    Kortenkamp, A., Casadevall, M., and da Cruz Fresco, P. (1996) The reductive conversion of the carcinogen chromium(VI) and its role in the formation of DNA lesions, Anals Clin. Laborat. Science 26, 160–175.Google Scholar
  85. 85.
    Borges, K.M. and Wetterhahn, K.E. (1989) Chromium cross-links glutathione and cysteine to DNA, Carcinogenesis 10, 2165–2168.CrossRefGoogle Scholar
  86. 86.
    Borges, K.M., Boswell, J.S., Liebross, R.H., and Wetterhahn, K.E. (1991) Activation of chromium(VI) by thiols results in chromium(V) formation, chromium binding to DNA and altered DNA conformation, Carcinogenesis 12, 551–561.CrossRefGoogle Scholar
  87. 87.
    Aiyar, J., Berkovits, H.J., Floyd, R.A., and Wetterhahn, K.E. (1991) Reaction of chromium(VI) with glutathione or with hydrogen peroxide: identification of reactive intermediates and their role in chromium(VI)-induced DNA damage, Env. Health Perspect. 92, 53–62.CrossRefGoogle Scholar
  88. 88.
    Tamino, G., Peretta, L., and Levis, A.G. (1981) Effects of trivalent and hexavalent chromium on the physicochemical properties of mammalian cell nucleic acids and synthetic polynucleotides, Chem. Biol. Interact. 37, 309–319.CrossRefGoogle Scholar
  89. 89.
    Pett, V., Sorof, J., Fenderson, M., and Zeff, L. (1985) The effect of chromium(III) upon thermal denaturation of DNA, Bioinorg. Chem. 13, 24–33.Google Scholar
  90. 90.
    Kortenkamp, A. and O’Brien, P. (1991) Studies of the binding of chromium(III) complexes to phosphate groups of adenosine triphosphate, Carcinogenesis 12, 921–926.CrossRefGoogle Scholar
  91. 91.
    Salnikow, K., Zhitkovich, A., and Costa, M. (1992) Analysis of the binding sites of chromium to DNA and protein in vitro and in intact cells, Carcinogenesis 13, 2341–2346.CrossRefGoogle Scholar
  92. 92.
    Lefevbre, Y. and Pézerat, H. (1992) Production of activated species of oxygen during the chromate(VI)-ascorbate reaction: implication in carcinogenesis, Chem. Res. Toxicol. 5, 461–463.CrossRefGoogle Scholar
  93. 93.
    Snow, E.T. (1994) Effects of chromium on DNA replication in vitro, Environ. Health Perspect. 102, 41–44(Suppl. 3).Google Scholar
  94. 94.
    Loeb, L.A. and Preston, B.D. (1986) Mutagenesis by apurinic/apyrimidinic sites, Ann. Rev. Genet. 20, 201–230.CrossRefGoogle Scholar
  95. 95.
    Bridgewater, L.C., Manning, F.C.R., and Patierno, S.R. (1994) Base-specific arrest of in vitro DNA replication by carcinogenic chromium: relationship to DNA interstrand crosslinking, Carcinogenesis 15, 2421–2427.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1997

Authors and Affiliations

  • A. Kortenkamp
    • 1
  • M. Casadevall
    • 2
  • P. Da Cruz Fresco
    • 3
  • R. O. J. Shayer
    • 1
  1. 1.Department of ToxicologyThe School of Pharmacy, University of LondonLondonUK
  2. 2.Gorlaeus LaboratoriesLeiden Institute of ChemistryLeidenThe Netherlands
  3. 3.Laboratorio de Farmacologia, Facultade de FarmaciaUniversidade do PortoPortoPortugal

Personalised recommendations