Trenbolone induces micronucleus formation and neoplastic transformation in Syrian hamster embryo fibroblasts but not in mouse C3H10T1/2 cells.
The synthetic androgen 17 beta-trenbolone (beta-TBOH), used as a growth promotant in cattle, and its metabolite 17 alpha-trenbolone (alpha-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 beta-TBOH and alpha-TBOH, but not testosterone nor its hormonally active metabolite, 5 alpha-dihydrotestosterone, caused a dose-related induction of micronuclei in SHE cells. In C3H10T1/2 cells, neither beta-TBOH nor alpha-TBOH gave rise to micronucleus induction. Furthermore, both beta-TBOH and alpha-TBOH, but not testosterone, were found to transform SHE cells but not C3H10T1/2 cells morphologically. The beta-TBOH-transformed SHE cells proved to be neoplastic in thymus-aplastic nude mice. These data show that beta-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 beta-TBOH are discussed.
Schiffmann
D
D
Institute of Pharmacology and Toxicology, University of Würzburg, Federal Republic of Germany.
Hieber
L
L
Schmuck
G
G
Pechan
R
R
Metzler
M
M
Henschler
D
D
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D006224:Cricetinae; D004963:Estrenes / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects; D005354:Fibrosarcoma / Q000139:chemically induced; D008647:Mesocricetus; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D015162:Micronucleus Tests; D014204:Trenbolone Acetate / Q000633:toxicity*
D004963:Estrenes; D014204:Trenbolone Acetate