Early changes in the radiosensitivity of Corynebacterium parvum-stimulated CFU-S

Abstract

Corynebacterium parvum injected intraperitoneally into C57BL mice induced a progression of hemopoietic CFU-S of C57BL mice from the resting state immediately after, and in the early period (approximately 8 h) after stimulation. Dose-response survival curves of the stimulated endogenous spleen CFU-S after the C. parvum injection revealed changing slopes or D0 of dose-response survival curves indicative of changing sensitivity states. Shortly after stimulation, the cells were sensitive to high specific-activity tritiated thymidine (HSATT) or hydroxyurea (HU), indicating they were in the DNA-S phase. This commenced shortly after the C. parvum injection. Beginning at about 6 h, sensitivity to HSATT disappeared and there was an increase in radiosensitivity. Sensitivity to vinblastine (VLB) also became evident at 7 h. This was consistent with beginning mitosis and mitotic cell sensitivity to VLB. A dose-response survival curve for the G2 phase CFU-S was determined using both HSATT and VLB to eliminate the DNA-S phase and mitotic cells. The radiosensitivities of the resting G1, S, and G1-S phase cells were determined by D0 to be 80, 105 and 85 rad, respectively, measured in vivo. G2 sensitivity using a combined HSATT and VLB method showed a complex, bending dose-response curve with a terminal D0 of 58 rad. CFU-S progression was blocked by the anti-histamine H2 receptor agent, metiamide.