Combined effect of procarbazine and ionizing radiation on mouse jejunal crypts

The interaction between procarbazine and gamma-radiation on animal survival and on cell proliferation in the jejunum of the mouse was investigated. Procarbazine (501 mg/kg) injected intraperitoneally enhanced the effect of the gastrointestinal radiation syndrome in whole-body lethality studies by reducing the 7-day LD50 by 269 rads. Similar lethality responses were noted whether the drug was administered immediately before or after irradiation. In a series of temporal response studies, 501 mg/kg procarbazine injected intraperitoneally affected intestinal crypt cell proliferative activity in a manner similar to the effect of 1,000 rads of gamma-radiation, by an increase to above-normal proliferative activity. The indices of proliferative activity employed were tritiated thymidine activity per milligram intestine, tritiated thymidine activity per crypt, labeled nuclei per crypt, and mitotic figures per crypt. When procarbazine was injected 15 min prior to irradiation, the crypt cell proliferative activity decreased but never recovered, thus indicating an enhanced response with combined treatment.