Effect of tetrandrine on micronucleus formation and sister-chromatid exchange in both in vitro and in vivo assays.
The genotoxicity of tetrandrine, a drug potentially useful for the treatment of silicosis, was studied using the micronucleus and the sister-chromatid exchange (SCE) assay systems. Cultured Chinese hamster lung (V79) cells were used for the in vitro micronucleus and sister-chromatid exchange studies. Mouse bone marrow was used for the in vivo micronucleus assay and mouse spleen cells for the in vivo/in vitro sister-chromatid exchange analysis. The results show that SCE levels in V79 and in spleen cells were significantly elevated by treatment with tetrandrine at doses above 0.08 mg/ml and 100 mg/kg bw, respectively. Increased tetradrine-induced SCE in vitro was metabolic activation dependent. Tetrandrine failed to induce micronuclei at any of the doses tested. A decrease of replicative index with an increase in the concentration of tetrandrine was found both in vitro and in vivo. These results indicate that tetrandrine is a weak indirect-acting genotoxicant.
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV 26505-2888.
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D000470:Alkaloids / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D044182:Benzylisoquinolines; D001711:Biotransformation; D001853:Bone Marrow / Q000187:drug effects / Q000648:ultrastructure; D002455:Cell Division / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D008875:Middle Aged; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D000470:Alkaloids; D044182:Benzylisoquinolines; C009438:tetrandrine