Collateral sensitivity of a methotrexate-resistant L1210 cell line to the vinca alkaloids

L1210 mouse leukaemia cell lines showing a 20,000-fold differential sensitivity to methotrexate have been shown to exhibit some collateral sensitivity to at least two of the vinca alkaloids, vinblastine and vindesine. Vinblastine is the more cytotoxic for both cell lines. The extent of the collateral sensitivity decreases in the order vindesine greater than vinblastine greater than vincristine. Total cellular uptake studies with radiolabelled methotrexate showed only a two- to three-fold greater incorporation in the sensitive line. On the other hand, a two-fold greater incorporation of labelled vincristine occurred in the resistant line. No significant difference in the uptake occurred following labelled vinblastine treatment by the two cell lines. It is unlikely that differences in uptake account for the altered drug responses observed in the two cell lines.