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The genotoxicity of trenbolone, a synthetic steroid

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Abstract

Trenbolone, a synthetic androgen is used as a growth promotant in animal husbandry. Because of its steroidal structure and properties it has been extensively evaluated in a series of in vitro and in vivo assays to assess its genotoxic and initiating properties. Both the parent molecule 17-beta-hydroxytrenbolone and its metabolite 17-alpha-hydroxytrenbolone, produced only in cattle, have been tested. 17-beta-hydroxy-trenbolone was not genotoxic in the Ames Salmonella/microsome assay, cytogenetics assays in human lymphocytes and CHO cells, a micronu cleus assay in CHO cells, a DNA repair synthesis assay in HeLa cells, mammalian cell mutation assays with CHO and V79 cells, the mouse micronucleus assay, rat bone marrow or spermatogonial cytogenetics assays or in a test for initiators in the rat. In the mouse lymphoma cell mutation assay with L 5178Y Tk±cells, equivocal responses were obtained, particularly at highly toxic concentrations. With 17-alpha-hydroxytrenbolone a weak positive response was obtained in the L5178Y Tk±assay, particularly at highly toxic concentrations. Negative results were obtained in the Ames Salmonella/microsome assay, the cytogenetics assays using both human lymphocytes in vitro and rat bone marrow in vivo, the DNA repair assay and in the CHO mammalian cell mutation assay. It was also negative in the in vivo test for initiators. From this extensive battery of data, and also taking into account published data on trenbolone, it is concluded that 17-alpha-hydroxytrenbolone and 17-beta-hydroxy-trenbolone are devoid of genotoxic activity and are not initiators of cancer.

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Abbreviations

β-TBOH:

17-beta-hydroxy-4,9,11-androstatrien-3-one

α-TBOH:

17-alpha-hydroxy-4,9,11-androstatrien-3-one

DES:

diethylstilboestrol

TFT:

triflurothymidine

UDS:

unscheduled DNA synthesis

SHE:

Syrian hamster embryo

DMSO:

dimethylsulphoxide

6TG:

6-thioguanine

PHA:

phytomaemagglutinin

CHO:

Chinese hamster ovary cells

V79:

Chinese hamster lung cells

HPRT:

hypoxanthine-guanine phosphoribosyl transferase

2-AAF:

2-acetylaminofluorene

20 MC:

20-methylcholanthrene

Mit C:

mitomycin C

EMS:

ethylmethane sulphonate

DEN:

diethylnitrosamine

Oestrad:

oestradiol

Nitrosomorph:

nitrosomorpholine

ethinyl oestr:

ethinyl oestradiol

References

  • Amacher DE, Paillet S, Ray V (1979) Point mutation at the thymidine kinase locus in L5178Y mouse lymphoma cells. Mutat Res 64: 391–406

    Google Scholar 

  • Ames BN, McCann J, Yamasaki E (1975) Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutat Res 31: 347–364

    Google Scholar 

  • Ashby J (1983) The distinction between genetic and non-genetic mechanisms in chemical carcinogenesis. In: Zbinden et al. (eds) Current problems in drug toxicology. John Libby Eurotext, Paris London

    Google Scholar 

  • Ashby J (1982) Hormones, cancer and short-term genotoxicity data. European Toxicity Forum Meeting, Geneva May 3–7, 1982, pp 339–346

  • Banduhn N, Obe G (1985) Mutagenicity of 2-benzimidazolecarbamate, diethylstilboestrol and oestradiol: Structural chromosomal aberrations, sister-chromatid exchanges, C-mitosis, polyploidies and micronuclei. Mutat Res 156: 199–218

    Google Scholar 

  • Barraud B, Lugnier A, Dirheimer G (1983) In vivo covalent binding to rat liver of trenbolone as compared to 17β-oestradiol, testosterone and zeranol. In: Meissonnier (ed) Anabolics in human production. Soregraph, France, pp 325–338

    Google Scholar 

  • Bradley MO, Bhuygan B, Francis MC, Lanagenbach R, Peterson A, Huberman E (1981) Mutagenesis by chemical agents in V79 Chinese hamster cells. Mutat Res 87: 81–142

    Google Scholar 

  • Clive D, Spector JFS (1975) Laboratory procedure for assessing specific locus mutations at the Tk locus in cultured L 5178Y mouse lymphoma cells. Mutat Res 31: 17–29

    Google Scholar 

  • Drevron C, Picoli C, Montesano R (1981) Mutagenicity assays of oestrogenic hormones in mammalian cells. Mutat Res 89: 83–90

    Google Scholar 

  • Evans HJ, O'Riordan (1975) Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen tests. Mutat Res 31: 135–148

    Google Scholar 

  • Heddle JA (1983) The induction of micronuclei as a measure of genotoxicity. A report of the US Environmental Protection Agency Gene-Tox Program. Mutat Res 123: 61–118

    Google Scholar 

  • Helton Ed, Casciano DA, Althaus ZR, Plant HD (1977) Metabolism of 17β-ethynylestradiol by intact liver parenchymal cells isolated from mouse and rat. J Toxicol Environ Health 3: 953–963

    Google Scholar 

  • Hsie AW, Casciano DA, Couch DB, Krahn DF, O'Neill JP, Whitefield BL (1981) The use of Chinese hamster ovary cells to quantify specific locus mutation and to determine mutagenicity of chemicals. A report of the gene-tox program. Mutat Res 86: 193–214

    Google Scholar 

  • Lang R, Redmann U (1979) Non-mutagenicity of some sex hormones in the Ames Salmonella/microsome mutagenicity test. Mutat Res 67: 361–365

    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 in vitro. Abstract, German Cancer Society, March 6–8 1985, Heidelberg

    Google Scholar 

  • Martin CN, McDermid AC, Garner RC (1978) Testing of known carcinogens and non-carcinogens for their ability to induce unscheduled DNA synthesis in HeLa cells. Cancer Res 38: 2621–2627

    Google Scholar 

  • Matter B, Schmid W (1976) Trenimon- induced chromosomal damage in bone marrow cells of six mamalian species, evaluated by the micronucleus test. Mutat Res 12: 417–425

    Google Scholar 

  • Rogers AW (1973) Techniques in autoradiography. Elsevier, Amsterdam

    Google Scholar 

  • Ruttenberg AM, Kim H, Fischbein JW, Hanssker JS, Wasserkrug HL, Seligman AM (1968) Histochemical and ultrastructural demonstration of γ-glutamyl transpeptidase activity. J Histochem Cytochem 17: 517–526

    Google Scholar 

  • Scheutwinkel M, Hude W v d, Bassler A (1986) Studies on the genotoxicity of the anabolic drugs trenbolone and zeranol. Arch Toxicol 59: 4–6

    Google Scholar 

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

    Google Scholar 

  • Schuppler J, Damme J, Schulte-Hermann R (1983) Assay of some endogenous and sex steroids for tumor-initiating activity in the rat liver using the Solt-Farber system. Carcinogenesis 4: 239–241

    Google Scholar 

  • Solt D, Farber E (1976) New principle for the analysis of chemical carcinogenesis. Nature 263: 701–703

    Google Scholar 

  • Stich HF, San RHC, Kawazoe Y (1971) DNA repair synthesis in mammalian cells exposed to a series of oncogenic and nononcogenic derivatives of 4-nitroquinoline oxide. Nature 229: 416–419

    Google Scholar 

  • White AD (1980) In vitro induction of SCE in human lymphocytes by epichlorohydrin with and without metabolic activation. Mutat Res 78: 171–176

    Google Scholar 

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Author notes

  1. Margaret Richold

    Present address: Unilever Research, Colworth Lab., ESL, MK 44 1 LQ, Sharnbrook, Bedford, England

Authors and Affiliations

  1. Huntingdon Research Centre, PE 18 6 ES, Huntingdon, Cambs., England

    Margaret Richold

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  1. Margaret Richold
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Richold, M. The genotoxicity of trenbolone, a synthetic steroid. Arch Toxicol 61, 249–258 (1988). https://doi.org/10.1007/BF00364846

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  • DOI: https://doi.org/10.1007/BF00364846

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