Kinetics of Haemopoietic Recovery in Endotoxin‐treated Mice

Abstract

Kinetics of mouse spleen colony forming units were studied after intra-peritoneal injection of 1 pglg body weight bacterial endotoxin S. typhosa. When these mice were used as unirradiated and sublethally irradiated donors, it was possible to study the effect of the endotoxin injection upon the cells. Use of the treated mice as irradiated recipients of normal cells gave information about the host effect.In treated unirradiated mice, the total nucleated cell and the CFU counts were disturbed, and 2 days later a large fraction of the CFU were found in the DNA synthesis (S) phase. This meant that injection of endotoxin generated factors affecting the kinetics of the CFU and triggering the resting CFU into the proliferative cycle. If then the mice were given supralethal irradiation and used as recipients of normal bone marrow cells, more CFU seeded to the spleen as compared to normal recipients; but the dip and the growth rate of the CFU were not changed. Hence the endotoxin-generated factors had been eliminated in 2 days.A total body sublethal irradiation by 400 rad X-ray 2 days after endotoxin injection reduced the post-irradiation dip in the recovery curve of the CFU, indicating that though the factors affecting the cell kinetics had been eliminated, the cycling CFU behaved like a growing population. During the first week, the growth rate of the CFU remained the same as in control irradiated mice. The growth rate of the spleen CFU of the endotoxin-treated mice slowed down during the second week, and their self-replicating ability was low. Fluctuations in the DNA synthesizing fraction of the spleen CFU suggested a variability in the ratio of the length of the S phase and the cell generation time.

Mouse Survival after 5- Fluorouracil treatment and the Role of Autophagic Clearance in Rapid Recovery

“…Moreover, bone marrow recovery is intrinsic to the hematopoietic progenitor cell compartment and is dependent on the autophagic cells that survive the effects of 5-FU. The current results agree with prior reports showing bone marrow recovery [2][3][4][5]14,15].…”

“…One of the most effective chemotherapy agents is 5-fluorouracil (5-FU), which competes with uracil during the synthesis of ribonucleic acid (RNA) and interferes with deoxyribonucleic acid (DNA) formation by blocking thymine production [1], preventing cell division. This selective effect on rapidly proliferating cells is the basis for its carcinostatic potency [2][3][4][5].…”

Effect of Corynebacterium parvum on hemopoietic stem‐cell kinetics

“…Bacterial endotoxins and killed bacterial suspensions can affect the size and the proliferative status of the animal hemopoietic stem-cell compartment (Vos et al, 1972;Toujas et al, 1972;Monette et al, 1972;Dazord et al, 1973;Lahiri, 1976;Pouillart et al, 1976). A suspension of heat-and formol-killed Corynebacterium parvum (C. parvum) has also been found to induce in the mouse pronounced changes in the number of femoral HSC (Eliopoulos, 1977).…”