The genotoxicity of trenbolone, a synthetic steroid.

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-hydroxy-trenbolone and its metabolite 17-alpha-hydroxy-trenbolone, 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 micronucleus 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-hydroxy-trenbolone 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.