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A single subcutaneous injection of a preparation of heat-killed Lactobacillus casei (LC 9018), given before or after irradiation, significantly increased the survival rate of mice that had received 8.5-Gy 137Cs whole-body gamma-irradiation. A similar radioprotective effect was observed when LC 9018 was administered within the period from 2 days before irradiation to 9 h after irradiation, the pre-irradiation treatment being slightly better than the post-irradiation treatment. Increases in the weight of the spleen and in the number of endogenous spleen colonies on days 8 and 12 after irradiation suggested that the radioprotective effect was based on enhanced recovery of hematopoietic tissues. The activity of macrophage colony-stimulating factor (M-CSF) in serum was rapidly increased by the treatment and was maintained at the elevated level for 13 days. At the same time, an increased level of M-CSF mRNA was detected in the livers of the treated mice. However, LC 9018 failed to save the lives of mice when administered 3 days after irradiation, although it increased serum M-CSF as effectively as noted above. The small advantage of the pre-irradiation over the post-irradiation treatment was not explained by the increases of metallothionein in the hematopoietic tissues of the treated mice.

X-irradiation-induced emesis was investigated in Suncus murinus, a house musk shrew. Whole body X-irradiation caused emesis, and the calculated ED50 value that induced emesis in 50% of animals was 429 cGy. At the irradiation dose of 800 cGy all the animals vomited 10.0 +/- 2.4 times with a latency of 20.0 +/- 2.9 min. The emetogenic effect of X-irradiation was dependent on the part of the body exposed. Abdominal X-irradiation at 1000 cGy caused emesis in all animals studied, whereas the same dose to the head had no emetogenic effect. We investigated several prophylactic methods against X-irradiation-induced emesis. Surgical vagotomy completely inhibited the emesis induced by 800 cGy X-irradiation. Emesis was also prevented by the subcutaneous administration of tropisetron (ICS 205-930, a selective serotonergic 5-HT3 receptor antagonist) with an ID50 value of 29 micrograms/kg. These results suggest that (1) suncus is a useful experimental animal for the study of radiation-induced emesis and the development of prophylactic drugs, (2) serotonin plays an important role in X-irradiation-induced emesis, and (3) X-irradiation-induced emesis is very similar to that caused by cancer chemotherapeutic agents.

The activity of macrophage colony-stimulating factor (M-CSF) was found in the culture supernatant of mouse parenchymal liver cell fractions in a bone marrow colony-forming assay. The activity of an M-CSF-like substance purified by a four-step procedure was neutralized by goat anti-mouse M-CSF antiserum. M-CSF mRNA was detected in cellular RNA prepared from cultured parenchymal liver cell fractions by Northern blot analysis and also in cultured parenchymal liver cells by in situ hybridization. These results indicate that parenchymal liver cells have the capacity to produce M-CSF. We discuss the role of M-CSF in hematopoiesis, the immune response, and other biological phenomena.

L . P3 cells grown in serum-free synthetic medium produced a colony-stimulating factor (CSF: a sialoglycoprotein stimulating proliferation of granulocyte-macrophage progenitor cells). Addition of tunicamycin (2 microgram/ml) or 2-deoxy-D-glucose (10 mM) to the culture neither decreased the yield of CSF relative to the cell number grown nor induced heterogeneity of the produced CSF. However, CSF produced in the presence of tunicamycin (CSF-tm) was about 23 percent smaller in its molecular weight than normally produced CSF (CSF-normal). Similarly, the addition of 2-deoxy-D-glucose resulted in the formation of a CSF (CSF-dGlc) which was about 16 percent smaller than CSF-normal. However, both CSF-tm and CSF-dGlc seemed to have retained sialic acid residues, because they were focused respectively at pH 4.2 and pH 3.7 upon isoelectric focusing, and both were converted to a pH 5.2 species by treatment with neuraminidase. In addition, CSF-tm was significantly less heat-stable than CSF-normal, whereas CSF-dGlc was only slightly less stable. These results suggest that complete glycosylation of the factor is not necessary for its production nor for its stimulatory action on the proliferation of myeloid stem cells, but is necessary for its maximal stabilization.