Interactions of radiation and 5-fluorouracil, cyclophosphamide or methotrexate in intestinal crypt cells

Abstract

The interactions of radiation and 5-fluorouracil (5-FU), cyclopbosphamide (CTX), or methotrexate (MTX) in mouse jejunal crypt cells were studied using the microcolony survival may. 5-FU given from 48 hr before to 24 hr after irradiation resulted in an almost constant, increased cell kill except at injection 6 hr after irradiation, which resulted in a more pronounced effect. CTX enhanced the radiation effect only when given simultaneously with or up to 3 br after irradiation. The effect of MTX, extremely dependent on the sequence and interval between drug administration and irradiation, was most prominent when administered 1 hr before irradiation. At this drug-radiation interval, the Do surprisingly increased by a factor of 2.4, whereas MTX 15 min before irradiation displaced the survival curve to the left without changing the D 0. The influence of MTX on the radiation response disappeared when the drug was given either % hr before or 3 hr after irradiation.