Induction of micronuclei in V79 cells by the anabolic doping steroids tetrahydrogestrinone and trenbolone.
The synthetic steroid tetrahydrogestrinone is a new "designer drug" and was recently detected to be illegally used in sports. It is chemically closely related to trenbolone that is known as an animal growth promoter. The potencies of trenbolone, tetrahydrogestrinone and testosterone to induce micronuclei in V79 cells in vitro were determined. CREST analysis was employed to differentiate between aneugenic or clastogenic mechanisms. Cytotoxicity and an influence on the cell cycle were assessed in parallel. Incubations with testosterone, at concentrations between 3 and 300 microM, failed to induce micronuclei. By contrast, tetrahydrogestrinone and trenbolone increased the rate of micronuclei significantly, up to a doubling of the micronuclei rate of untreated controls. Tetrahydrogestrinone and trenbolone displayed a bell-shaped dose-response curve, with maximal effects observed at 3 and 30 microM, respectively. The micronuclei induced by tetrahydrogestrinone and trenbolone were predominantly kinetochor (CREST) positive, pointing to an aneugenic mode of action. This may be related to the specific structure of both molecules with a system of activated double bonds. As the genotoxic effect of tetrahydrogestrinone at a chromosomal level appears at a low concentration range, it cannot be ruled out that tetrahydrogestrinone presents a genotoxic hazard on a chromosomal level under conditions of its current misuse in sports.
Dorn
Susanne B
SB
Leibniz Research Centre for Working Environment and Human Factors, Institut für Arbeitsphysiologie an der Universität Dortmund (IfADo), Dortmund, Germany.
Bolt
Hermann M
HM
Thevis
Mario
M
Diel
Patrick
P
Degen
Gisela H
GH
D045930:Anabolic Agents / Q000009:adverse effects*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005867:Gestrinone / Q000009:adverse effects / Q000031:analogs & derivatives*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D014204:Trenbolone Acetate / Q000009:adverse effects*
D045930:Anabolic Agents; D005867:Gestrinone; C479553:tetrahydrogestrinone; D014204:Trenbolone Acetate