Corynebacterium parvum-Induced Radiosensitivity and Cycling Changes of Hematopoietic Spleen Colony-Forming Units1. 2

ABSTRACT-Ten days after total·body irradiation with 550 rads of 80Co, spleen colonies were observed in adult C57BL mice. A change in radiosensitivity induced by Corynebacterium parvum, as measured by increased numbers of colony·forming units that survived the 550 rads, began shortly after C. parvum stimulation and extended for at least 7 days before irradiation. C. parvum given 4-24 hours before, followed by high specific activity eHlthymidine (HSATT) 1 hour before total·body irradiation great· Iy reduced survival of the stem cells that formed spleen colonies (CFUs) and CFUs radiosensitivity to control levels. The HSATT sensitivity by "suicide " assay in vivo and the time·response change in radiosensitivity corresponded with the decrease in radiosensitivity, which showed that CFUs were stimulated by C. parvum administration and entered the S·phase shortly after stimulation. The data indicated a resting population close to the S·phase. After stimulation, this population entered S·phase. Syngeneic mouse lymphoma cells injected iv 24 hours earlier did not elicit any effect as a stimulus to CFUs radiosensitivity change.-J Nat! Cancerlnst59: 173-177,1977. Corynebacterium parvum has been known to have an an-titumor action (1) and has been proposed as an active nonspecific stimulant of the immune system (2-4). It also stimulates the hematopoietic system (5-7), lymphocytes (8), and the macrophage-reticuloendothelial systems (2, 9-11). Investigators have shown that C. parvum stimulates host resistance against tumor growth in experimental animals and sometimes produces complete regression of antigenic tumors (1, 4). In an effort to study the action of C. parvum on the hematopoietic stem cells, these investigations were undertaken with the use of the endogenous spleen CFU system and concern the marked changes observed in CFUs radiosensitivity after administration of the vaccine. The ac-tion was rapid, apparent in several hours, and appeared to be due to cell cycle progression of CFUs