The in vivo interaction between vincristine and radiation in a C3H mammary carcinoma and the feet of CDF 1 mice

Abstract

Purpose : Evaluation of the interaction between vincristine (VCR) and X rays in a murine tumor and its surrounding skin. Methods and Materials : End points were local tumor control and moist desquamation using the C3H mammary carcinoma and the mouse foot skin in vivo. Cell cycle effects of VCR was studied by dual parameter flowcytometry. Vincristine was administered as a single IP injection at various time intervals from 4 days before to 4 days after irradiation. Results : Flowcytometric studies of cell cycle distribution showed that VCR caused a temporary blockage of cells in the mitotic phase; the proportion of cells in GZM increased three-fold at intervals up to 48 h after VCR treatment. The radiation enhancement peaked when VCR was administered 24 h before X rays in tumors, and when given 15 min before X rays in skin. A significant therapeutic gain was observed at the 24 h preirradiation or postirradiation intervals—the therapeutic gain factors being 1.19 and 1.24, respectively ( p < 0.005). Analysis of the tumor data suggested an additive cytotoxic effect rather than VCR radiosensitization. In contrast to what was expected from the single dose data, a significant loss of therapeutic effect was found for the addition of VCR administered at the first day of a fractionated irradiation regime with five fractions in 5 days ( P < 0.025). Conclusion : The tumor control studies showed a lack of correlation between the VCR-induced accumulation of cells in G 2M cell cycle phase and enhancement of tumor radiation response. Preirradiation VCR caused radiosensitization both in tumors and skin, whereas postirradiation VCR mostly resulted in responses equal to radiation only.