Effect of tetrandrine on micronucleus formation and sister-chromatid exchange in both in vitro and in vivo assays.
Xing SG; Shi XC; Wu ZL; Whong W-Z; Ong T
Mutat Res 1989 Sep; 224(1):5-10
The genotoxic effects of tetrandrine (518343) were investigated through the micronucleus and sister chromatid exchange (SCE) assay systems. Groups of Chinese-hamsters and CD-mice received single intraperitoneal doses of 50, 100, and 200mg/kg tetrandrine. Cultured Chinese-hamster lung (V79) cells were used for in-vitro versions of the assays. CD-mouse bone marrow cells were used in the in-vivo micronucleus assay; spleen cells were used in the in- vitro/in-vivo SCE study. Hamster cells were incubated with tetrandrine for 3 hours, fixed and stained, and evaluated for SCEs. Cytokinesis block by cytochalasin-B was used to create micronucleus slides after the V79 cells were exposed to 10 to 40 micrograms per milliliter (microg/ml) tetrandrine in the absence or presence of activation by a 2 hour tetrandrine treatment. Mouse femoral marrow cells and spleen cells were also prepared as stained slides for microscopic evaluation. SCE frequency increased in metabolically activated hamster cells with tetrandrine doses of 80mocrog/ml or more. Micronucleus formation in hamster and mouse cells, in-vitro and in-vivo, exhibited no effect. Dose dependent increases in mononucleated cells and decreases in binucleated cells were seen in cytochalasin-B blocked hamster cells. An increase in the ratio of polychromatic erythrocytes to normochromatic erythrocytes was seen in mouse bone marrow cells. Doses of tetrandrine of between 30 and 40microg/ml were toxic to most of the nonstimulated hamster cells; almost half the mice treated with 200mg/kg died. The authors conclude that tetrandrine is a weak genotoxic agent.
NIOSH-Author; Laboratory-animals; In-vivo-study; In-vitro-study; Genotoxic-effects; Cytotoxicity; Dose-response; Chromosome-damage;
Author Keywords: Tetrandrine; Genotoxicity; Mammalian cell; Primary cell