Biometals

, Volume 12, Issue 2, pp 131–139 | Cite as

Apoptosis and p53 gene expression in male reproductive tissues of cadmium exposed rats

  • Guogang Xu
  • Guangqian Zhou
  • Taiyai Jin
  • Tong Zhou
  • Sten Hammarstrüm
  • Anders Bergh
  • Gunnar Nordberg
Article

Abstract

Reverse transcription (RT) PCR technique was used to investigate the mechanism of apoptosis induced by Cd and the change of its related genes in testes and prostate of rats. Adult male rats were given a single (s.c.) injection of CdC l2 0, 2.5, 5.0, 10 μmol/kg. 48 h and 72 h after administration of Cd, animals were sacrificed. The results indicated that Cd can induce apoptosis in testes via p53-independent pathway. No apoptosis occurred in prostate in any of the Cd-exposed groups. There was a clearly negative relationship in testes between p53 gene expression and Cd exposure and this dose-response relationship was observed both at 48 h and 72 h. There was a very small increase of this gene expression in the dorsolateral lobe of the prostate in Cd exposed groups. The other apoptosis related gene, bcl-x, was not detectable in either control or Cd-exposed group in testes and dorsal prostate. Although the MT-I gene was expressed in testes or dorsal prostate both in control and exposed groups, no overexpression of MT-I gene was found after administration of Cd . The expression of MT-I in the ventral prostate was not detected in the control group, but a weak expression was found after Cd exposure. Since p53 is a tumo r suppressor gene which can inhibit tumorigenesis, the consequence of a Cd-induced decrease of p53 in testes may have a relation to the known risk of Cd tumorigenesis in this tissue.

cadmium apoptosis RT-PCR p53 gene expression testes rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abel, J., Ruiter, N. and Kuhn-Velten, W.N. 1991 Comparative study on metallothionein induction in whole testicular tissue and isolated Leydig cells. Arch. Toxicol. 65, 228-234.Google Scholar
  2. Azzouzi, A.E., Tsangaris, G. T., Pellegrini, O., Manuel, Y., Benveniste, J. and Thomas, Y. 1994 Cadmium induces apoptosis in a human T cell line. Toxicology 88, 127-139.Google Scholar
  3. Boise, L.H., Gonzalez-Garcia, M., Postema, C.E., et al. 1993 bcl-x, a bcl-2-related gene that function as a dominant regulator of apoptotic cell death. Cell 74, 597-608.Google Scholar
  4. Clarke, A.R., Purdie, C.A., Harrison, D.J., et al. 1993 Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362, 849-852.Google Scholar
  5. De, K.S., Enders, G.C. and Andrews, G.K. 1991 High levels of metallothionein messenger RNAs in male germ cells of adult mouse. Mol. Endocrinol. 5, 628-635.Google Scholar
  6. Ghatak, S., Oliveria, P., Kaula, P. and Ho S-mei. 1996 Expression and regulation of metallothionein mRNA levels in the prostates of Nobel rats: lack of expression in the ventral prostate and regulation by sex hormones in the dorsolateral prostate. Prostate 29, 91-100.Google Scholar
  7. Gunn, S.A, Gould, T.C. and Anderson, W.A.D. 1963 Cadmium induced interstitial cell tumors in rats and mice and their prevention by zinc. J. Natl. Cancer Inst. 31, 745-752Google Scholar
  8. Gunn, S.A. and Gould, T.C. 1970 Cadmium and other mineral elements. In: A.D. Johnson, W.R. Gomes and N.L. Vandemark (eds), The Thesis. Academic Press, New York, pp. 377-481.Google Scholar
  9. Hollstein, M., Sidransky, D., Vogeistein, B., and Harris, C.C. 1991 p53 mutations in human cancers. Science 253, 49-53.Google Scholar
  10. Kuerbitz, S.J., Plunkett, B.S., Walsh, W.B. and Kastan, M.B. 1992 Wild-type p53 is a cell cycle checkpoint determination following irradiation. Proc. Natl. Acad. Sci. USA 89, 7491-7495.Google Scholar
  11. Lane, D.P. (1992) p53, Guardian of the genome. Nature 358, 15-16.Google Scholar
  12. Livingstone, L.R., White, A., Sprouse, J., Livanos, E., Jacks, T., and Tisty, T.D. 1992 Altered cell cycle arrest and gene amplification potential accompany loss of wild type p53. Cell 70, 923-935.Google Scholar
  13. Lowe, S.W., Schmitt, E.M., Osborne, B.A., and Jacks, T. 1993 p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362, 847-849.Google Scholar
  14. Mckenna, I.M., Bare, R.M. and Waalkes, M.P. 1996 Metallothionein gene expression in testicular interstitial cells and liver of rats treated with cadmium. Toxicology 107, 121-130.Google Scholar
  15. Nolan, C.V. and Shaikh, Z.A. 1986 An evaluation of tissue metallothionein and genetic resistance to cadmium toxicity in mice. Toxicol. Appl. Pharmacol. 85, 135-144.Google Scholar
  16. Nordberg, G.F. 1971 Effects of acute and chronic cadmium exposure on the testicle of mice. Environ. Physiol. 1, 171-187.Google Scholar
  17. Nordberg, G.F. 1972 Cadmium metabolism and toxicity: Experimental studies on mice with special reference to the use of biological materials as indices of retention and the possible role of metallothionein in transport and detoxification of cadmium. Environ. Physiol. Biochem. 2, 7-36.Google Scholar
  18. Parizek, J. 1957 The destructive effect of cadmium ion on testicular tissue and its prevention by zinc. J. Endocrinol. 15, 56-63.Google Scholar
  19. Sambrook, J., Fritsch, E. F. and Maniatis, T. 1989 Analysis and cloning of eukaryotic genomic DNA: isolation of DNA from mammalian cells. In: Molecular Cloning, 2nd edn., Cold Spring Harbor Laboratory Press, New York, pp 9.14-9.19.Google Scholar
  20. Shankland, S.J. and Scholey, J.W. 1994 Expression of transforming growth factor-ß1 during diabetic renal hypertrophy. Kidney Int. 46, 430-442.Google Scholar
  21. Shaw, P., Bovey, R., Tardy, S., Sshli, R., Sordat, B., and Costa, J. 1992 Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc. Natl. Acad. Sci. USA 89, 4495-4499.Google Scholar
  22. Shiraishi, N., Uno, H., and Waalkes, M.P. 1993a Effect of L-ascorbic acid pretreatment on cadmium toxicity in the male Fisher (F344/NCr) rat. Toxicology 85, 85-100.Google Scholar
  23. Shiraishi, N., Barter, R., Uno, H. and Waalkes, M.P. 1993b Effect of progesterone pretreatment on cadmium toxicity in the male Fisher (F344/NCr) rat. Toxicol. Appl. Pharmacol. 118, 113-118.Google Scholar
  24. Shiraishi, N. and Waalkes, M.P. 1994 Enhancement of metallothionein gene expression in male Wistar (WF/NCr) rats by treatment with calmodulin inhibitors: Potential role of calcium regulatory pathway in metallothionein induction. Toxic. Appl. Pharmacol. 125, 97-103.Google Scholar
  25. Strasser, A., Harris, A.W., Jacks, T. and Cory, S. 1994 DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by bcl-2. Cell 79, 329-339.Google Scholar
  26. Schwarts D., Goldfinger N., and Rotter V. 1993 Expression of p53 protein in spermatogenesis is confined to the tetraploid pachytene primary spermatocytes. Oncogene 8, 1487-1494.Google Scholar
  27. Symonds, H., Krall., L., Remington, L., et al. 1994 p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell 78, 703-711.Google Scholar
  28. Waalkes, M.P., Rehm, S., Riggs, C.W., et al. 1988 Cadmium carcinogenesis in male Wistar [Crl:(WI)BR] rats: dose-response analysis of tumor induction in the prostate and testes and at the injection site. Cancer Res. 48, 4656-4663.Google Scholar
  29. Waalkes, M.P., Coogan, T.P., and Barter, R.A. 1992 Toxicological principles in metal carcinogenesis with special emphasis on cadmium. Crit. Rev. Toxicol. 22, 175-201Google Scholar
  30. Waalkes, M.P. and Rehm, S. 1994 Cadmium and prostatic cancer. J. Toxicol. Environ. Health 43, 251-259Google Scholar
  31. Westin P, Brändström A, Damber JE and Bergh A. 1995 Castration plus oestrogen treatment induces but castration alone suppresses epithelial cell apoptosis in an androgen-sensitive rat prostatic adenocarcinoma. Br. J. Cancer 72,140-145Google Scholar
  32. Will K., Warnecke, G., Bergmann, S. and Deppert, Wolf G. 1995 Species-and tissue-specific expression of the C-terminal alternatively spliced form of the tumor suppressor p53. Nucleic Acids Res. 23, 4023-4028.Google Scholar
  33. Xu, C., Johnson, J.E., Singh, P.K., Jones, M.M., Yan, H. and Carter, C.E. 1996 In vivo studies of cadmium-induced apoptosis in testicular tissue of the rat and its modulation by a chelating agent. Toxicology 107, 1-8.Google Scholar
  34. Yin, Y., Tainsky, M.A., Bischoff, F.Z., Strong, L.C., and Wahl, G.M. 1992 Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutation alleles. Cell 70, 937-948.Google Scholar
  35. Yonish-Rouach, E., Resnitsky, D., Lolem, J., Sachs, L., Kimchi, A., and Oren, M. 1991 Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature 352, 345-347.Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Guogang Xu
    • 1
    • 2
  • Guangqian Zhou
    • 3
  • Taiyai Jin
    • 1
    • 2
  • Tong Zhou
    • 1
    • 2
  • Sten Hammarstrüm
    • 3
  • Anders Bergh
    • 4
  • Gunnar Nordberg
    • 4
  1. 1.Department of Occupational and Environmental MedicineUmeå UniversityUmeåSweden
  2. 2.Department of Industrial Health and Occupational DiseaseShanghai Medical UniversityShanghaiPeople's Republic of China
  3. 3.Department of ImmunologyUmeå UniversityUmeåSweden
  4. 4.Department of PathologyUmeå UniversityUmeåSweden

Personalised recommendations