The effect of pre- or post-treatment with a calmodulin inhibitor (trifluoperazine) on the response to cytotoxic agents of cells within small EMT6/Ca/VJAC spheroids.

Treatment of small EMT6 spheroids (approximately 250 microns in diameter) with trifluoperazine (TFP), a calmodulin inhibitor, before drug exposure did not alter cellular response to adriamycin (ADM) (5 micrograms/ml), CCNU (5 micrograms/ml) or vincristine (VCR) (1 micrograms/ml). The cell killing effect of nitrogen mustard (HN2) was, however, suppressed by TFP pre-treatment even when the TFP was removed before HN2 exposure. Treatment of small spheroids with TFP for 24 hr after drug exposure was found to have no effect on recovery from potentially lethal damage (PLDR) following bleomycin (BLM) (40 micrograms/ml), CCNU (5 micrograms/ml), HN2 (1 micrograms/ml), or X rays (9 Gy). The surviving fraction measured immediately after drug exposure (SF-0) and the surviving fraction with 24 hr delayed assay (SF-24) for cells within small spheroids were similar following 1 hr exposure to ADM. Following 3 hr ADM exposure, however, the SF-24 was less than the SF-0. If TFP was present during the 24 hr period after drug exposure, a considerable decrease in SF-24 compared to SF-0 was seen in both cases.