Effect of teniposide (VM-26) on the cell survival, micronuclei-induction and lactate dehydrogenase activity on V79 cells.
The genotoxic effect of 0, 1, 5, 10, 25, 50 and 100 nM teniposide (VM-26) treatment was studied on cultured V79 cells. Treatment of V79 cells with different concentrations of teniposide resulted in a concentration-dependent decline in the cell survival and growth kinetics. VM-26 treatment also caused alteration in the cell proliferation kinetics as evidenced by the increase in the frequency of mononucleate cells, with a consequent decline in the frequency of binucleate cells in a concentration-dependent manner at all the post-treatment time periods. Exposure of V79 cells to different concentrations of VM-26 resulted in a concentration related elevation in the frequency of micronucleated binucleate (MN) cells. The frequency of MN was significantly higher in VM-26 treated cells than that of non-drug treated cells at all the post-treatment time periods. A peak frequency of MN was observed at 16 h post-treatment that declined thereafter. The release of lactate dehydrogenase increased with the increase in drug concentration and a maximum LDH release was observed at 0.5 h post-treatment after exposure to 10-100 nM VM-26. While a peak value was observed at 1 and 2 h for 5 and 1 nM VM-26, respectively. The biological response was evaluated by determining the relationship between micronuclei and cell survival. The cell survival declined with increasing MN frequency, resulting in a close but an inverse relationship between the cell survival and micronuclei-induction. The dose effect relationships for micronuclei induction, LDH release and biological response was linear quadratic.
Adiga
S K
SK
Department of Radiobiology, Kasturba Medical College, India.
Jagetia
G C
GC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D013713:Teniposide / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013713:Teniposide; D007770:L-Lactate Dehydrogenase