Azidothymidine induces dose dependent increase in micronuclei formation in cultured HeLa cells

Exposure of HeLa cells to azidothymidine (AZT) resulted in a concentration dependent decline in growth kinetics. 100 microM of AZT completely inhibited the cell growth. The frequency of binucleate and multinucleate cells declined with increasing concentration of AZT and the formation of multinucleate cells was completely inhibited at 20 and 30 h at higher concentrations indicating inhibition of cell division. Similarly, the clonogenicity of cells declined in a concentration dependent manner and 10 microM AZT killed 50% of the cells. Conversely, the frequency of MNBNC (micronucleated binucleate cell) increased in a concentration dependent manner and was significantly higher in the AZT treated group than the non-drug treated control group. The relationship between concentrations of AZT and micronuclei-induction was linear for all the post-treatment time periods studied. The biological response was also determined by plotting the surviving fraction of cells on the X-axis and the number of micronuclei on the Y-axis. A close and inverse correlation between the surviving fraction and micronuclei formation was observed and the data could be fitted on to a linear quadratic model.