Vincristine increases the genomic instability in irradiated cultured human peripheral blood lymphocytes

Increase in the genomic instability by 10 ng of vincristine (VCR) pretreatment was studied in cultured human peripheral blood lymphocytes exposed to 0, 0.5, 1, 2, and 3 Gy gamma radiation by the micronucleus assay. The frequency of micronucleated binucleate lymphocytes (MNBNC) increased in a dose dependent manner after exposure to different doses of gamma radiation and the dose response was linear. The pre-treatment of lymphocytes with 10 ng/ml VCR caused a further elevation in the frequency of MNBNC and this was significantly greater than that of the concurrent PBS pre-treated irradiated lymphocytes. The dose response for VCR treated group was linear up to 1 Gy irradiation. A further increase in the radiation dose resulted in a decline in the induction of MNBNC in VCR pretreated irradiated group, although it was significantly higher than the PBS treated irradiated group. VCR pretreatment not only increased the frequency of MNBNC with one micronuclei but also the frequency of MNBNC with 2, 3 and 4 MN significantly, indicating the increase in the multiple sites of damage to DNA by VCR pre-treatment. This increase in multiple MNBNC was also dose dependent, however, the dose response was linear quadratic.