Trenbolone growth promotant: covalent DNA binding in rat liver and in Salmonella typhimurium, and mutagenicity in the Ames test.
DNA binding in vivo: [6,7-3H]beta-trenbolone (beta-TBOH) was administered p.o. and i.p. to rats. After 8 or 16 h, DNA was isolated from the livers and purified to constant specific radioactivity. Enzymatic digestion to deoxyribonucleotides and separation by HPLC revealed about 90% of the DNA radioactivity eluting in the form of possible TBOH-nucleotide adducts. The extent of this genotoxicity, expressed in units of the Covalent Binding Index, CBI = (mumol TBOH bound per mol nucleotide)/(mmol TBOH administered per kg body weight) spanned from 8 to 17, i.e. was in the range found with weak genotoxic carcinogens. Ames test: low doses of beta-TBOH increased the number of revertants in Salmonella strain TA100 reproducibly and in a dose-dependent manner. The mutagenic potency was 0.2 revertants per nmol after preincubation of the bacteria (20 min at 37 degrees C) with doses between 30 and 60 micrograms per plate (47 and 94 micrograms/ml preincubation mixture). Above this dose, the number of revertants decreased to control values, accompanied by a reduction in survival. The addition of rat liver S9 inhibited the mutagenicity. DNA binding in vitro: calf thymus DNA was incubated with tritiated beta-TBOH with and without rat liver S9. Highest DNA radioactivities were determined in the absence of the "activation" system. Addition of inactive S9 (without cofactors) reduced the DNA binding by a factor of up to 20. Intermediate results were found with active S9. DNA binding in Salmonella: beta-TBOH was irreversibly bound to DNA isolated from S. typhimurium TA100 after incubation of bacteria with [3H]beta-TBOH.
Lutz
W K
WK
Institute of Toxicology, ETH, Schwerzenbach, Switzerland.
Deuber
R
R
Caviezel
M
M
Sagelsdorff
P
P
Friederich
U
U
Schlatter
C
C
D000818:Animals; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000633:toxicity*; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats; D011919:Rats, Inbred Strains; D012307:Risk Factors; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism; D014204:Trenbolone Acetate / Q000378:metabolism / Q000633:toxicity*
D004963:Estrenes; D009153:Mutagens; D004247:DNA; D014204:Trenbolone Acetate