Indian Journal of Clinical Biochemistry

, Volume 16, Issue 2, pp 145–152 | Cite as

Cadmium, carcinogen, co-carcinogen and anti carcinogen

  • Ramesh Chandra
  • Sujata K. Dass
  • Priyanka Tomar
  • Manisha Tiwari


As a stress agent, inducing apoptosis and blocking it, Cd can have both helpful and harmful effects. The atmosphere is a thin envelope which makes the worid a global village. Cd is the most toxic metal in air. As both the first and second messenger of the stress response, it is synergistically toxic with all other stressors, including many other carcinogens. Elimination of Pb and its replacement with added benzene in gasoline appears to have increased the toxicity of atmospheric Cd. With scientific understanding of the molecular basis of Cd's role in carcinogenesis and anti-carcinogenesis, primary cancer prevention can be practiced by reducing Cd and chemical air pollution and educating the public on smoke cessation, healthy eating habits and stress reduction. Using the existing information on Cd and its effects, determinations could be made on established cancers so that individualized treatment protocols can be developed to improve patient care.


Cadmium Carcinogen Co-carcinogen Anti-carcinogen 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Noda, H., Sugiyama, M., Tatsumi, S., Sano, Y., Konishi, S., Furutani, A. and Yoshimura, M. (1993) Study on secular changes of cadmium concentration accumulated in main organs of Japanese. Nippon Hoigaku Zasshi 47 (121), 153–159.PubMedGoogle Scholar
  2. 2.
    Elinder, C. Q. (1992) Cadmium as an environmental hazard. IARC Sci. Publ. 118, 1232–1243.Google Scholar
  3. 3.
    Ochi, T., Takahashi, K. and Ohsawa, M. (1987) Indirect evidence for the induction of a prooxidant state by cadmium chloride in cult red mammalian cells and a possible mechanism or the induction. Mut. Res. 180, 257–266.Google Scholar
  4. 4.
    Kopp, S. J., Dear, A. A., and Prentice, R. C. (1986) 31P NMR studies of the intact perfused rat heart: a novel analytical approach for determining functional-metabolic correlates, temporal relationships, and intracellular actions of cardiotoxic chemicals non-destructively in an intact organ model. Toxicol. Appl. Pharmacol. 82, 200–210.PubMedCrossRefGoogle Scholar
  5. 5.
    Toury, R., Boissonneau, E. and Stelly, N. (1985) Mitochondrial alterations in Cd2+-treated rats: general regression of inner membrane cristae and electron transport impairment. Biol. Cell 55, 71–86.PubMedGoogle Scholar
  6. 6.
    Smith, J. B., Dwyer, S. D. and Smith, L. (1989) Evidence for a cell surface receptor that cadmium stimulates and zinc antagonizes. J. Biol. Chem. 264, 7115–7118.PubMedGoogle Scholar
  7. 7.
    Von Zglinicki, T., Edwall, C., Ostiund, E., Und B., Nordberg, M., Ringertz, N. R. and Wroblewski, J. (1992) Very low cadmium concentrations stimulate DNA synthesis and cell growth. J. Cell. Sci. 103 IPt 41, 1073–1081.Google Scholar
  8. 8.
    Furst, A. and Nickel, V. S. (1989) Cadmium carcinogenicity in the same Fischer-344 rat. Proc. Ann. Meet. Am. Assoc. Cancer Res. 30: A 532.Google Scholar
  9. 9.
    Freedman, L. P., Luisi, B. F. and Korszun, Z. R. (1988) Function and structure of the metal coordination sites with the glucocorticoid DNA binding domain. Nature 334, 543–546.PubMedCrossRefGoogle Scholar
  10. 10.
    Gedamu, L., Varshney, U., Jahroudi, N. and Foster, R. (1987) Structure and expression of the human metallothionein genes. Experientia Suppl. 52, 361–372.PubMedGoogle Scholar
  11. 11.
    Jin, P. and Ringertz, N. R. (1990) Cadmium induces transcription of proto-oncogenes c-jun and c-myc in rat L6 myoblasts. J. Biol. Chem. 265, 14061–14065.PubMedGoogle Scholar
  12. 12.
    Waalkes, M. P. and Rehm, M. S. (1994) Cadmium and prostate cancer. J. Toxicol. Environ. Health 43 (3) 251–269.PubMedGoogle Scholar
  13. 13.
    Waalkes, M. P., Anver, M. and Diwan, B. A., (1999) Carcinogic effects of cadmium in the noble (NBL/cr) rat: induction of pituitary, testicular and injection site tumors and intraepithelial proliferative lessions of the dorsal prostate toxicol. Sci. 52 (2), 154–161.Google Scholar
  14. 14.
    Hainaut, P. and Milner, J. (1993) A structural role for metal ions in the ‘wild-type’ conformation of the tumor suppressor protein p53. Can. Res. 53, 1739–1742.Google Scholar
  15. 15.
    Pearson, C. A. and Prozialeck, W. C. (2001) E-Cadherin, beta-catenin and cadmium carcinogenesis. Med. Hypotheses. 56 (5), 573–581.PubMedCrossRefGoogle Scholar
  16. 16.
    Waalkes, M. P. (2000) Cadmium carcinogenesis in review J. Inorg. Biochem. 79 (1–4), 241–244.PubMedCrossRefGoogle Scholar
  17. 17.
    Kasahara, K., Fujiwara, Y., Nishio, K., Ohmori, T., Sugimoto, Y., Komiya, K. Matsuda, T. and Saijo, N. (1991) Metallothionein content correlates with the senstivity of human small cell lung cancer cell lines to cisplatin. Can. Res. 51, 3237–3242.Google Scholar
  18. 18.
    Ripla, B. and Chandra, R. (1993) Effect of metal salts, organometals and metalloporphyrins on heme synthesis and catabolism with special reference to clinical implications and interactions with cytochrome p-450. Drug Metabol. Rev. 25, 49–152.CrossRefGoogle Scholar
  19. 19.
    Sunderman, F. W. Jr. (1987). Metal Induction of heme oxygenase. Ann. N. Y. Acad. Sci. 514, 65–80.PubMedCrossRefGoogle Scholar
  20. 20.
    Moore, M., Narasimhan, T. R., Wang, X, Krishnan, V., Safe, S., Williams, H. J. and Scott, A. I. (1993) Interaction of, 12-0-tetradecanoylphorbol-13-acetate (TPAI and 17 beta estradiol in MCF-7 human breast cancer cells. J. Ster. Biochem. Mol. Biol. 44, 251–261.CrossRefGoogle Scholar
  21. 21.
    Lohmann, R. D. and Beyersmann, D. (1993) Cadmium and zinc mediated changes of the Ca2+ I-dependent endonuclease in apoptosis. Biochem. Biophys. Res. Commun. 190, 1097–1103.PubMedCrossRefGoogle Scholar
  22. 22.
    Chandra, R., Beri, R. and Sarkar, A. (1992) Effect of hepatic DNA, RNA, and protein synthesis in rats bearing transplanted tumor by Dalton's Lymphoma Cells. J. Inorg. Biochem. 48 (1), 1–14.PubMedCrossRefGoogle Scholar
  23. 23.
    Chandra, R., Beri, R. and Sarkar, A. (1992) Synthesis and characterization of iron (III), cobalt (II) and nickel (II) metal complexes with TaHh-DAP and Ta-Hh-TDA hexadentate macrocyclic ligands. Synth. Rect. Inorg. Metal-org. Chem. 22 (8), 1195–1209.CrossRefGoogle Scholar
  24. 24.
    Waalkes, M. P., Diwan, B. A., Weghorst, C. M., Bare, R. M., Ward, J. M. and Rice, J. M. (1991) Anticarcinogenic effects of cadmium in B6C3F1 mouse liver and lung. Toxicol. Appl. Pharmacol. 110 (21), 327–335.PubMedCrossRefGoogle Scholar
  25. 25.
    Horiguchi, H., Mukaida, N., Okamoto, S., Teranishi, H., Kasuya, M. and Matsushima, K.. (1993) Cadmium induces interleukin-8 production in human peripheral blood mononuclear cells with the concommitant generation of superoxide radicals. Lymphokine and Cytokine Res. 12, 421–428.Google Scholar
  26. 26.
    Thompson, E. W., Brunner N., Torri, J., Johnson, M. D., Boulay, V., Wright, A., Uppman, M. E., Steeg, P. S. and Clarke, R. (1993) The invasive and metastatic properties of hormone-independent but hormone-responsive variants of MCF-7 human breast cancer cells. Clin. Exp. Metastasis 11, 15–26.PubMedCrossRefGoogle Scholar
  27. 27.
    Brown, D. and Van Beneden, R. J. (1993) Investigations of molecular mechanisms of gonadal tumors in herbicide-exposed bivalves. Proc. Ann. Meet. Am. Assoc. Canc. Res. 34, A 1001.Google Scholar
  28. 28.
    Muller, L. and Stacey, N. H. (1988) Subcellular toxicity of low level cadmium in rats: effect on cytochromec oxidase. Toxicol 9, 223–224.Google Scholar
  29. 29.
    Ebeling, P. and Komsto, V. K. Physiological importance of dehydroepiandrosterone (1994) Lancet 343, 1479–1481.PubMedCrossRefGoogle Scholar
  30. 30.
    Shirai, T., Iwasaki, S., Masui, T., Mori, T., Kato, T. and Ito, N. (1993) Enhancing effect of cadmium on rat ventral prostate carcinogensis induced by 3′, 2′-dimethyl-4-aminobiphenyl. Jap. J. Canc. Res. 84, 1023–1030.Google Scholar
  31. 31.
    Harrison, P. T. and Heath, J. C. (1986) Apparent synergy in lung carcinogenesis, Interactions between N-nitrosoheptamethyleneimine, particulate cadmium and crocidolite asbestos fibers in rats. Carcinogenesis 7, 1903–1908.PubMedCrossRefGoogle Scholar
  32. 32.
    Martin Mateo, M. C., Rabadan, J. and Boustamante, J (1990) Comparative analysis of certain metals and tumor markers in bronchopulmonary cancer and colorectal cancers. Metals and tumor markers in the neoplastic process. Clin. Physiol. Biochem. 8, 261–266.PubMedGoogle Scholar
  33. 33.
    Collins, J. J., Strauss, M. E., Levinskas, G. J. and Conner, P. R. (1993) The mortality experience of workers exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in a trichlorophenol process accident. Epidemiol. 4, 7–13.CrossRefGoogle Scholar
  34. 34.
    Sens, M. A., Hazen-Martin, D. J., Bylander, J. E. and Sens, D. A. (1994) Heterogeneity in the amount of lonic cadmium necessary to elicit cell death in independent cultures of human proximal tubule cells. Toxicol. Lett. 70, 185–191.PubMedCrossRefGoogle Scholar
  35. 35.
    Chandra, R., Dhawan, M. and Malhotra, R. (1995) Regulation Of hepatic heme oxygenase by CoMP. J. Inorg. Biochem. 59 (2&3), 516–535.CrossRefGoogle Scholar
  36. 36.
    Koizumi, T. U. (1992) Role of oxidative stress in single dose cadmium-induced testicular cancer. J. Toxicol. Environ. Health. 37, Ul, 25–36.PubMedCrossRefGoogle Scholar
  37. 37.
    Iversen, P. L. and Ebadi, M. (1992) Antisense oligonucleotide-mediated inhibition of metallothionein protein synthesis In: Neuroblastoma IMR 32 and Chang liver cells in culture. Biol. Signals 1121, 57–64.CrossRefGoogle Scholar
  38. 38.
    Zhang, Z. J., Troll, W., Koenig, K. L. and Frenkel, K. (1990) Carcinogenic sulfide salts of nickel and cadmium induce H, O, formation by human polymorphonuclear leukocytes. Canc. Res. 50, 7564–7570.Google Scholar

Copyright information

© Association of Clinical Biochemists of India 2001

Authors and Affiliations

  • Ramesh Chandra
    • 1
  • Sujata K. Dass
    • 1
  • Priyanka Tomar
    • 1
  • Manisha Tiwari
    • 1
  1. 1.Dr. B. R. Ambedkar Center for Biomedical ResearchUniversity of DelhiDelhi

Personalised recommendations