Pretreatment of mice with 50-1000 micrograms of the bacterial extract Broncho-Vaxom (BV, free of endotoxin) before sublethal irradiation induced an increase in the number of endogenous haemopoietic stem cells (E-CFU). The degree of radioprotection was dependent on both the time of administration and the dose of BV. An optimal E-CFU survival was observed when 500 micrograms of BV was administered i.p. 24 h before irradiation. BV did not affect the day 9 CFU-S survival in the bone marrow directly after irradiation. However, 5, 9 and 12 days after irradiation, the number of day 9 CFU-S was almost 2-fold higher in the bone marrow of BV injected mice. Pretreatment with BV protected C57B1/6 mice in a dose-dependent manner from the lethal effect of ionizing radiation. A single dose (50, 100, 250, or 500 micrograms) of bacterial lysate injected i.p. 24 h before 9.5 Gy gamma-rays (LD100/21) protected 16%, 25%, 80%, and 94% of C57B1/6 mice, respectively. The dose reduction factor in the case when the BV (500 micrograms per mouse) was administered at that time was 1.18 (95% CL 1.12, 1.25).
The effects of the bacterial extract broncho‐vaxom (BV; radioprotective immunomodulator; 500 μg/mouse i.p., 24 h) and indomethacin (INDO; inhibitor of prostaglandin production; 2 times 40 μg/mouse i.m., ‐ 24 h and ‐ 3 h) on the post‐irradiation recovery of hemopoietic functions in mice were investigated. Both agents were administered either alone or in combination. Endogenous spleen colony formation was increased in all treatment groups, with combination‐treated mice exhibiting the greatest effects. Similarly, 24 h after combined administration of BV and INDO (i.e. at the time of presumed irradiation) to the non‐irradiated mice granulocyte‐macrophage colony‐forming cell (GM‐CFC) numbers were greater in the bone marrow and spleen. Also, as determined by hydroxyurea injection, there was an increase in the number of GM‐CFC in the S‐phase of the cell cycle in the bone marrow. However, GM‐CFC in the spleen of combination pretreated mice was not stimulated to significant proliferation as compared to GM‐CFC in the spleen of mice injected with BV alone. Combined modality treatment was also more effective than single agent treatments in accelerating bone marrow cellularity and GM‐CFC regeneration, but not in accelerating GM‐CFC regeneration in the spleen. Combined administration of BV and INDO to mice prior to lethal irradiation exerted an additional radioprotective effect and protected 95% of the C57B1/6 mice.
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