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

Abstract

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.

17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone) exhibits tissue selective anabolic activity: effects on muscle, bone, adiposity, hemoglobin, and prostate

“…In our studies, TREN administration resulted in a nearly complete ablation of circulating testosterone and DHT, the primary endogenous androgens implicated in prostate growth, through mechanisms apparently associated with feedback inhibition; however, we did not directly evaluate the possibility that TREN may initiate or accelerate prostate cancer growth. Several previous reports indicate that trenbolone appears to produce little genotoxic activity and is not an initiator of cancer in various in vitro models (47,51), although trenbolone has been shown capable of inducing morphological changes in the Syrian hamster embryo cell transformation assay (an in vitro mutagenicity model) (50,51). As such, future research examining the effects of TREN and other androgens using in vitro and/or in vivo xenograft models of androgen-responsive prostate cancer is warranted and should be conducted prior to this agent being advanced to clinical testing.…”

Risk Assessment of Growth Hormones and Antimicrobial Residues in Meat

“…TBA is a weak toxic chemical with an oral LD50 of 1,000~1,500 mg/kg bw. The genotoxicities of TBA, 17α-trenbolone, and 17β-trenbolone were negative in various in vitro and in vivo assays (Ingerowski et al, 1981 ; Lutz et al, 1988 ; Schiffman et al, 1988) . In carcinogenicity studies, TBA given by feeding induced liver hyperplasia in mice at 0.9~9 mg/kg bw/day and islet-cell tumours of the pancreas in rats at 1.85 mg/kg bw/day, as a consequence of the hormonal activity of TBA (Schiffman et al, 1985 , 1988) .…”

“…The genotoxicities of TBA, 17α-trenbolone, and 17β-trenbolone were negative in various in vitro and in vivo assays (Ingerowski et al, 1981 ; Lutz et al, 1988 ; Schiffman et al, 1988) . In carcinogenicity studies, TBA given by feeding induced liver hyperplasia in mice at 0.9~9 mg/kg bw/day and islet-cell tumours of the pancreas in rats at 1.85 mg/kg bw/day, as a consequence of the hormonal activity of TBA (Schiffman et al, 1985 , 1988) . At a higher level of 2 μg/kg bw/day in pigs, TBA induced hormonal effects involving decreased testosterone levels in the serum of male pigs; reductions in weights of the testes, ovaries, and uteri; atrophy of testicular interstitial cells; suppression of cyclic ovarian activity; absence of glandular development of the uterine endometrium; and lack of alveolar development and secretion in the mammary glands (JECFA, 1988 ; van Leeuwen, 1993) .…”

Hormone Use in Food Animal Production: Assessing Potential Dietary Exposures and Breast Cancer Risk

“…As the most active form of TBA, TB is the predominant focus of the toxicologic literature. In contrast to assessments of its endocrine effects, genotoxicity assays of TB have produced mostly negative results [12], although a number of these tests were conducted by the industry [24], and some positive experiments have been reported as well [25,26]. TB has induced neoplastic transformations in Syrian hamster embryo cells in vitro in multiple experiments [25,27,28].…”