Skip to main content
Log in

Transformation of prostatic epithelial cells and fibroblasts with cadmium chloride in vitro

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Primary cultures of fibroblasts and epithelial cells were established from rat ventral prostate (RVP), canine (CP), baboon (BP), and human (HP) prostates, and were used in an assay system to evaluate cadmium chloride (CdCl2) cytotoxicity in vitro. Fibroblasts were always more susceptible to CdCl2 cytotoxicity than the epithelial cells of the same species. There was a distinct species variability to CdCl2 cytotoxicity, with RVP cells being greater than 200 times more susceptible than HP. Primary cultures treated with CdCl2 were subcultivated to establish cell lines. Only RVP fibroblast and epithelial cells resulted in permanent cell lines. Two fibroblast and two epithelial cell lines were derived from CdCl2-treated RVP cell cultures. The epithelial cell lines possessed tonofilaments, desmosomes and keratin. All four cell lines were resistant to CdCl2, had different karyotypes and an excess of chromosome 13. These results demonstrate the transforming potential of cadmium on prostate cells. The role of metallothionein and the significance of extra chromosomes 13 are discussed as possible factors of cadmium resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Amacher DE, Paillet SC (1980) Induction of trifluorothymidineresistant mutants by metal ions in L5178Y/TK+/-cells. Mutat Res 78: 179–288

    Google Scholar 

  • Beach LR, Palmiter RD (1981) Amplification of the metallothionein-I gene in cadmium-resistant mouse cells. Proc Natl Acad Sci USA 78: 2110–2114

    Google Scholar 

  • Bernard A, Lauwerys R (1984) Cadmium in human population. Experientia 40: 143–146

    Google Scholar 

  • Bracken WM, Sharma RP, Kleinschuster SJ (1984) Cadmium accumulation and subcellular distribution in relation to cadmium chloride induced cytotoxicity in vitro. Toxicology 33: 93–102

    Google Scholar 

  • Casto BC, Meyers J, DiPaolo JA (1979) Enhancement of viral transformation for evaluation of the carcinogenic or mutagenic potential of inorganic metal salts. Cancer Res 39: 193–198

    Google Scholar 

  • Committee for a Standardized Karyotype of Rattus norvegicus (1975) Standard Karyotype of the Norway rat, Rattus norvegicus. Cytogenet Cell Genet 12: 199–205

    Google Scholar 

  • Corrigan AJ, Huang PC (1981) Cellular uptake of cadmium and zinc. Biological Trace Elements Res 3: 197–216

    Google Scholar 

  • Costa M, Heck JD, Robison SM (1982) Selective phagocytosis of crystalline metal sulfide particles and DNA strand breaks as a mechanism for the induction of cellular transformation. Cancer Res 42: 2757–2763

    Google Scholar 

  • DeKundt G, Deminatti M (1978) Chromosome studies in human lymphocytes after in vitro exposure to metal salts. Toxicology 10: 67–75

    Google Scholar 

  • DiPaolo JA, Casto BC (1979) Quantitative studies of in vitro morphological transformation of Syrian hamster cells by inorganic metal salts. Cancer Res 39: 1008–1013

    Google Scholar 

  • Douglas WHJ, Terracio L, Glass H (1980) Isolation, culture and characterization of epithelial cells derived from rat ventral prostate. Anat Rec 197: 239–256

    Google Scholar 

  • Durnam DM, Palmiter RD (1981) Transcriptional regulation of the mouse metallothionein-1 gene by heavy metals. J Biol Chem 256: 5712–5716

    Google Scholar 

  • Durnam DM, Palmiter RD (1984) Induction of metallothionein-I mRNA in cultured cells by heavy metals and iodoacetate: Evidence for gratuitous inducers. Mol Cell Biol 4: 484–491

    Google Scholar 

  • Enger MD, Ferzoco LT, Tobey RA, Hildebrand CE (1981) Cadmium resistance correlated with cadmium uptake and thionein binding in CHO cell variants Cd220F4 and Cdr30F9. J Toxicol Environ Hlth 7: 675–690

    Google Scholar 

  • Evans R, Mark SR, Patierno D, Wang O, Cantoni, Costa M (1983) Growth inhibition and metallothionein induction in cadmium-resistant cells by essential and non-essential metals. Mol Pharmacol 24: 77–83

    Google Scholar 

  • Fassett DW (1975) Cadmium: Biological effects and occurrence in the environment. Ann Rev Pharmacol 15: 425–435

    Google Scholar 

  • Fox MRS (1983) Cadmium bioavailability. Fed Proc 42: 1726–1729

    Google Scholar 

  • Gasiorek K, Bauchinger M (1981) Chromosome changes in human lymphocytes after separate and combined treatment with divalent salts of lead, cadmium and zinc. Environ Mut 3: 513–518

    Google Scholar 

  • Gick GG, McCarty KS (1982) Amplification of the metallothionein-I gene in cadmium- and zinc-resistant Chinese hamster ovary cells. J Biol Chem 257: 9049–9053

    Google Scholar 

  • Gick GG, McCarty KS, Jr., McCarty KS Sr (1981) The role of metallothionein synthesis in cadmium- and zinc-resistant CHO-KLM cells. Exp Cell Res 132: 23–30

    Google Scholar 

  • Gunn SA, Gould TC, Anderson WAD (1963) Cadmium-induced interstitial cell tumors in rats and mice and their prevention by zinc. J Natl Cancer Inst 31: 745–759

    Google Scholar 

  • Guthrie J (1964) Histological effects of intratesticular injection of cadmium chloride in domestic fowls. Br J Cancer 18: 255–260

    Google Scholar 

  • Haddow A, Roe FJC, Dukes CE, Mitchley BCV (1964) Cadmium neoplasia: sarcomata at the site of injection with cadmium sulphate in rats and mice. Br J Cancer 18: 667–671

    Google Scholar 

  • Hallenbeck WH (1984) Human health effects of exposure to cadmium. Experientia 40: 136–142

    Google Scholar 

  • Heath JC, Daniel MR, Dingle JT, Webb M (1962) Cadmium as a carcinogen. Nature 193: 592–593

    Google Scholar 

  • Hildebrand CE, Cram LS (1979) Distribution of cadmium in human blood cultures in low levels of CdCl2. Accumulation of Cd in lymphocytes and preferential binding to metallothionein. Proc Soc Exp Biol Med 161: 438–443

    Google Scholar 

  • Hildebrand CE, Griffith JK, Tobey RA, Walters RA, Enger MD (1981) Molecular mechanisms of Cd detoxification in Cd-resistant cultured cells: Role of Metallothionein and other inducible factors. In: E. C. Foulkes (Ed) The biological role of metallothionein. Elsevier, Amsterdam, pp 279–303

    Google Scholar 

  • Holt D, Magos L, Webb M (1980) The interaction of cadmium-induced rat renal metallothionein with divalent mercury in vitro. Chem Biol Interact 32: 125–135

    Google Scholar 

  • IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Vol. 2. Some Inorganic and Organometallic Compounds. Lyon, France: International Agency for Research on Cancer, pp 17–47, 74–99, 126–149

  • Kanematsu N, Hara M, Kada T (1980) Rec assay and mutagenicity studies on metal compounds. Mutat Res 77: 109–116

    Google Scholar 

  • Karin M, Eddy RL, Henry WM, Haley LL, Byers MC, Shows TB (1984) Human metallothionein genes are clustered on chromosome 16. Proc Natl Acad Sci USA 81: 5494–5498

    Google Scholar 

  • Kazantzis G (1963) Induction of sarcoma in the rat by cadmium sulfide pigment. Nature (Lond) 198: 1213–1214

    Google Scholar 

  • Kjellstrom T (1979) Exposure and accumulation of cadmium in populations from Japan, the United States, and Sweden. Environ Health Perspect 28: 169–197

    Google Scholar 

  • Kolonel LN (1976) Association of cadmium with renal cancer. Cancer 37: 1782–1787

    Google Scholar 

  • Lane PW, Eicher EM (1979) Gene order in linkage group XVI of the house mouse. J Hered 70: 239–244

    Google Scholar 

  • Levan G (1974a) Nomenclature for G-bands in rat chromosomes. Hereditas 77: 37–52

    Google Scholar 

  • Levan G (1974b) The detailed chromosome constitution of a benzypyrene-induced rat sarcoma: A tentative model for G-band analysis in solid tumors. Hereditas 78: 273–290

    Google Scholar 

  • Morselt AFW, Copuis Peerboom-Stegeman JHJ, Jonstra-Spaapen EJ, James J (1983) Investigation of the mechanism of cadmium toxicity at cellular level. Arch Toxicol 52: 91–97

    Google Scholar 

  • Nishioka H (1975) Mutagenic activities of metal compound in bacteria. Mutat Res 31: 185–189

    Google Scholar 

  • Oberly TJ, Piper CE, McDonald DS (1982) Mutagenicity of metal salts in the L5178Y mouse lymphoma assay. J Toxicol Environ Health 9: 367–376

    Google Scholar 

  • Ochi T, Ishiguro T, Ohsawa M (1983) Participation of active oxygen species in the induction of DNA single-stranded scissions by cadmium chloride in cultured Chinese hamster cells. Mutat Res 122: 169–175

    Google Scholar 

  • Ochi T, Mogi M, Watanabe M, Ohsawa M (1984) Induction of chromosomal aberrations in cultured Chinese hamster cells by short-term treatment with cadmium chloride. Mutat Res 137: 103–109

    Google Scholar 

  • Ochi T, Ohsawa M (1983) Induction of 6-thioguanine-resistant mutants and single-strand scission of DNA by cadmium chloride in cultured Chinese hamster cells. Mutat Res 111: 69–78

    Google Scholar 

  • Ofner P, Terracio L, Vena RL (1984) Androgen metabolism in cultured prostatic cells. In: New Approaches to the Study of Benign Prostatic Hyperplasia. Alan R. Liss, Inc. New York. Prog Clin Biol Res 145: 363–380

  • Ofner P, Vena RL, Terracio L, Douglas WHJ (1982) Comparative C19-radiosteroid metabolism in primary monolayer cultures of epithelial cells and fibroblasts from rat ventral and canine prostate and rat lung. J Androl 3: 269–280

    Google Scholar 

  • Paton G, Allison A (1972) Chromosome damage in human cell cultures induced by metal salts. Mutat Res 16: 332–336

    Google Scholar 

  • Piscator M (1981) Role of cadmium in carcinogenesis with special reference to cancer of the prostate. Environ Health Perspect 40: 107–120

    Google Scholar 

  • Rivedal E, Sanner T (1981) Metal salts as promoters of in vitro morphological transformation of hamster embryo cells initiated by benzo(a)pyrene. Cancer Res 41: 2950–2953

    Google Scholar 

  • Rohr G, Bauchinger M (1976) Chromosome analysis in cell cultures of the Chinese hamster after application of cadmium sulphate. Mutat Res 40: 125–130

    Google Scholar 

  • Rugstad HE, Norseth T (1975) Cadmium resistance and content of cadmium-binding protein in cultured human cells. Nature (Lond) 257: 136–137

    Google Scholar 

  • Rugstad HE, Norseth T (1978) Cadmium resistance and content of cadmium-binding protein in two enzyme-deficient mutants of mouse fibroblasts (L-cells). Biochem Pharmacol 27: 647–650

    Google Scholar 

  • Sanwal MC, Sing RD, Alverson G, Srivasta LS, Sholiton LJ (1978) Decreased testosterone synthesis in zinc deficient and cadmium exposed rats. Fed Proc 37: 890–896

    Google Scholar 

  • Shiraishi Y, Kurahashi H, Yoshida TH (1972) Chromosomal aberrations in cultured human leukocytes induced by cadmium sulfide. Proc Jpn Acad 48: 133–137

    Google Scholar 

  • Sunderman FW Jr (1977) Metal carcinogenesis. In: R. A. Goyer and M. A. Mehlamm (eds.). Advances in modern toxicology. Vol. 1, Washington, D. C., Hemisphere Publishing Comp. pp 257–295

    Google Scholar 

  • Suzuki S, Taguchi T, Yokohashi G (1969) Dietary factors influencing upon the retention rate of orally administered 115m CdCl2 in mice, with special reference to calcium and protein concentration in diet. Ind Hlth 7: 155–162

    Google Scholar 

  • Takenaka S, Oldiges H, Konig H, Hochrainer D, Oberdorster G (1983) Carcinogenicity of cadmium chloride aerosols in W rats. J Natl Cancer Inst 70: 367–373

    Google Scholar 

  • Terracio L, Douglas WHJ (1982) Densitometric and morphometric evaluation of growth in primary cultures of rat ventral prostate epithelial cells. The Prostate 3: 183–191

    Google Scholar 

  • Terracio L, Douglas WHJ, Pennachio D, Vena RL, Ofner P (1982) Primary epithelial cell cultures derived from canine prostate: Isolation, culture and characterization. Am J Anat 164: 311–332

    Google Scholar 

  • Umeda M, Nishimura M (1979) Inducibility of chromosomal aberrations by metal compounds in cultured mammalian cells. Mutat Res 67: 221–229

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Terracio, L., Nachtigal, M. Transformation of prostatic epithelial cells and fibroblasts with cadmium chloride in vitro. Arch Toxicol 58, 141–151 (1986). https://doi.org/10.1007/BF00340973

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00340973

Key words

Navigation