Flow-cytometric analysis of DNA distribution after VP16-213 treatment of Lewis lung carcinoma

The two dosage schedules of VP16 that gave the least and the greatest efficacy in Lewis lung carcinoma of the mouse were selected for evaluation of the cytokinetic effects observable in vivo at different intervals after treatment (schedule A: 40 mg/kg IV, on day 8 after transplant; schedule B: 13 mg/kg IV, repeated on days 8, 11 and 14 after transplant). After the single dose and after each repeated dose there was a marked increase in the percentage of cells in the LS-G₂-M phases, with a corresponding decrease in the percentage of cells in G₀-G₁. The number of neoplastic tetraploid cells compared with normal diploid cells in the tumor was reduced after the single IV dose, and more markedly so after repeated doses. This study suggests that the more marked delay of cancer cell growth and greater effectiveness observed with schedule B is related to repeated blockade of the LS-G₂-M phases.