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Trenbolone induces micronucleus formation and neoplastic transformation in Syrian hamster embryo fibroblasts but not in mouse C3H10T1/2 cells

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Abstract

The synthetic androgen 17β-trenbolone (β-TBOH), used as a growth promotant in cattle, and its metabolite 17α-trenbolone (α-TBOH) were tested for genetic toxicity in Syrian hamster embryo (SHE) cells and in mouse C3H10T1/2 embryo fibroblasts by measuring the induction of micronucleus formation and neoplastic cell transformation. Both β-TBOH and α-TBOH, but not testosterone nor its hormonally active metabolite, 5α-dihydrotestosterone, caused a dose-related induction of micronuclei in SHE cells. In C3H10T1/2 cells, neither β-TBOH nor α-TBOH gave rise to micronucleus induction. Further more, both β-TBOH and α-TBOH, but not testosterone, were found to transform SHE cells but not C3H10T1/2 cells morphologically. The β-TBOH-transformed SHE cells proved to be neoplastic in thymus-aplastic nude mice. These data show that β-TBOH is able to cause changes at the chromosomal level and neoplastic transformation independent of its hormonal activity in one mammalian cell system but not in another one. The implications of these data for the risk evaluation of β-TBOH are discussed.

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Abbreviations

TBOH:

trenbolone, 17-hydroxy-4,9,11-androstat-rien-3-one

DES:

diethylstilbestrol, E-3,4-di(p-hydroxyphenyl) hex-3-ene

DMSO:

dimethylsulfoxide

PCS:

fetal calf serum

PBS:

phosphate-buffered saline pH 7.4 (0.14 MNaCl, 3 mM KCl, 8 mM Na2HPO4, 1 mM KH2PO4)

SHE:

Syrian hamster embryo

References

  • Barraud B, Lugnier A, Dirheimer G (1984) Determination of the binding of trenbolone and zeranol to rat-liver DNA in vivo as compared to 17β-oestradiol and testosterone. Food Addit Contam 1: 147–155

    Google Scholar 

  • Barrett JC, Wong A, McLachlan JA (1981) Diethylstilbestrol induces neoplastic transformation without measurable gene mutation at two loci. Science 212: 1402–1404

    Google Scholar 

  • Berwald Y, Sachs L (1965) In vitro transformation of normal cells to tumor cells by carcinogenic hydrocarbons. J Natl Cancer Inst 35: 641–657

    Google Scholar 

  • DiPaolo JA, Nelson RL, Donovan PJ (1971) Morphological, oncogenic and karyological characterization of Syrian hamster embryo cells transformed in vitro by carcinogenic polycyclic hydrocarbons. Cancer Res 31: 1118–1127

    Google Scholar 

  • Hoffmann B, Evers P (1986) Anabolic agents with sex hormone like activities: problems of residues. In: Rico AG (ed) Drug residues in animals. Academic Press Inc, New York, pp 111–146

    Google Scholar 

  • Ingerowski GH, Scheutwinkel-Reich M, Stan HJ (1981) Mutageni city studies on veterinary anabolic drugs with the Salmonella/ microsome test. Mutat Res 91: 93–98

    Google Scholar 

  • Lutz WK, Caviezel M, Marinovich M, Friederich U, Schlatter C (1985) Investigation of mutagenicity and of the potential for binding of trenbolone to DNA in rat liver and in vitro. J Cancer Res Clin Oncol 109: A 16

    Google Scholar 

  • Kommission der Europäischen Gemeinschaften (1984) Berichte des Wissenschaftlichen Veterinärausschusses, des Wissen-schaftlichen Futtermittelausschusses und des Wissenschaftli-chen Lebensmittelausschusses auf der Grundlage des Berichtes der Wissenschaftlichen Gruppe „Anabolika in der tierischen Erzeugung“, ISBN 92-825-5038-9, EGKS-EWG-EAG, Luxemburg: Amt für amtliche Veröffentlichungen der Euro-päischen Gemeinschaften

    Google Scholar 

  • Pienta RJ (1980) Transformation of Syrian hamster embryo cells by diverse chemicals and correlation with their reported car cinogenic and mutagenic activities. In: de Serres FJ, Hollaen der A (eds) Chemical mutagens. Principles and methods for their detection. Plenum Press, New York, vol 6, pp 175–202

    Google Scholar 

  • Pienta RJ, Poiley JA, Lebherz WB III (1977) Morphological transformation of early passage golden Syrian hamster embryo cells derived from cryopreserved primary cultures as a reliable in vitro bioassay for identifying diverse carcinogens. Int J Cancer 19: 642–655

    Google Scholar 

  • Pottier J, Cousty C, Heitzman RJ, Reynolds IP (1981) Differences in the biotransformation of a 17β-hydroxylated steroid, trenbolone acetate, in rat and cow. Xenobiotica 11: 489–500

    Google Scholar 

  • Reznikoff CA, Bertram JS, Brankow DW, Heidelberger C (1973) Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of cell division. Cancer Res 33: 3239–3249

    Google Scholar 

  • Richold M (1988) The genotoxicity of trenbolone, a syntheti6c steroid. Arch Toxicol 61: 249–258

    Google Scholar 

  • Schiffmann D, Metzler M, Neudecker T, Henschler D (1985) Morphological transformation of Syrian hamster embryo cells by the anabolic agent trenbolone. Arch Toxicol 58: 59–63

    Google Scholar 

  • Schiffmann D, Lieb G, Metzler M, Henschler D (1986) Induction of micronuclei in Syrian hamster embryo (SHE) fibroblasts by diethylstilbestrol (DES) and related compounds. Toxicol Lett 31 (Suppl): 204

    Google Scholar 

  • Schulte-Hermann R, Timmermann-Trosiener I, Schuppler J (1983) Promotion of spontaneous preneoplastic cells in rat liver as a possible explanation of tumor production by non mutagenic compounds. Cancer Res 43: 839–844

    Google Scholar 

  • Tsutsui T, Maizumi H, McLachlan JA, Barrett JC (1983) Aneu-ploidy induction and cell transformation by diethylstilbestrol: a possible chromosomal mechanism in carcinogenesis. Cancer Res 43: 3814–3821

    Google Scholar 

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This study has been supported by a grant from the Bundesministerium für Jugend, Familie, Frauen und Gesundheit

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Schiffmann, D., Hieber, L., Schmuck, G. et al. Trenbolone induces micronucleus formation and neoplastic transformation in Syrian hamster embryo fibroblasts but not in mouse C3H10T1/2 cells. Arch Toxicol 62, 49–53 (1988). https://doi.org/10.1007/BF00316257

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  • DOI: https://doi.org/10.1007/BF00316257

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