VP 16 activity was investigated on cells derived from primary tumor or metastases of Lewis lung carcinoma grown in vitro. After 24 hr exposure to VP 16 we found a marginal effect at 0.1 μg/ml, but at 1 and 10 μg/ml [3H]-TdR uptake was 37 and 85% less than controls for primary tumor and 43 and 83% for metastases; cell numbers dropped to 41 and 76% of controls for primary tumor and 30 and 68% for metastases. After 72 hr exposure VP 16 had a similar effect on cells of primary tumor or metastases, but a cytotoxic effect was already evident at 0.01 μg/ml and increased proportionally to the concentration reaching virtual complete cell killing at 1 μg/ml. This study suggests that the much greater in vivo sensitivity to VP 16 of metastases than primary tumor of Lewis lung carcinoma probably arises less from an intrinsically greater susceptibility of metastatic cells than from pharmacokinetic factors.
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