Hemopoietic Death Research Articles

Effect of whole body hyperthermia (39°C, 1 h) on radiation-induced apoptosis in Swiss mice

Mild whole body hyperthermia (WBH) treatment when given prior to radiation exposure is known to protect mice against radiation-induced hemopoietic death. This radioprotective effect seems to be mediated through WBH-induced cytokines and growth factors. Exposure to total body irradiation (TBI) also induces cell death by apoptosis in animal cells. The present studies were therefore carried out to investigate whether WBH pretreatment could protect mice against radiation-induced apoptotic death. The extent of apoptosis in bone marrow cells derived from mice at different time intervals after WBH, TBI and whole body hyperthermia treatment given 20 h prior to total body irradiation (WBH+TBI) treatments was studied by three independent methods namely DNA ladder assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay and caspase-3 assay. The studies have revealed that the mild WBH treatment (39°C, 1 h) when given 20 h prior to TBI (8 Gy) results in reduction in TBI-induced apoptosis. The results imply that WBH-induced impairment of apoptosis may have some role in WBH-induced radioprotection in Swiss mice.

Increased lethality and delay in the recovery of hemopoietic stem cells after irradiation in mice exposed to nitrous oxide

Effects of N2O-exposure on the survival rate and growth kinetics of hemopoietic stem cells after irradiation were investigated. LD 50, 30 days after irradiation, was 300 rad for N2O exposed mice and over 550 rad for control mice. Recovery of the pluripotent hemopoietic stem cells (CFU-S) and granulocyte-macrophage progenitor cells (GM-CFC) was significantly delayed in the spleen of N2O-exposed mice after 150 rad irradiation, compared to that of control mice. However, in bone marrow, there was a significant but slight difference in the recovery of GM-CFC and no significant difference in the recovery of CFU-S between the two groups. These results suggest that N2O augments the damage of splenic hemopoiesis in irradiated mice, and this may be responsible for the increased hemopoietic death.

Radiobiological evaluation of a newly synthesized cysteamine derivative

A new cysteamine-based compound, 1109 (N-glycylglycyl-S acetylcysteamine trifluoroacetate) was tested on both normal tissues and tumors to evaluate its radioprotective potential. 1109, which is three times less toxic than WR-2721, was injected at a dose approximately equal to half the LD50(30 days). The Protection Factor (PF = γ ray dose ratio) after whole body irradiation was 1.3 – 1.4 for intestinal death and 1.4 – 1.5 for hemopoietic death when intervals of 40 or 20 min elasped between injection and the end of irradiation. A crypt cell assay was done for both 1109 and WR-2721; PFs were 1.1 and 1.4, respectively. 1109 was then tested on five solid tumors. For each cell line (4 human, 1 murine) one dose of radiation was delivered. Surviving fraction ratios with and without drug ranged between 2.4 and 14.1 when an interval of 20 min elapsed between injection and the end of irradiation. The degree of radioprotection proved time dependent for EMT6 and HRT18; radioprotection afforded by WR-2721 on these tumors is either similar or greater than radioprotection afforded by 1109 depending on the time interval between injection and irradiation.

Radiation-Induced Hemopoietic Death in Mice as a Function of Photon Energy and Dose Rate

Radiation-induced hemopoietic death was measured in mice exposed to photons of four different energies: 250-kVp X rays, 60Co gamma rays (1.25 MeV), and 6- and 25-MV photons from a linear accelerator. For each radiation source, the lethal dose which killed 50% of the population in 30 days (LD50/30) associated with the hemopoietic syndrome was determined in groups of mice exposed to graded doses from 600 to 1150 cGy at dose rates of 20, 40, and 80 cGy/min. The calculated LD50/30 values for 25 and 6 MV were significantly different from each other at all exposure rates while no difference was observed between 6 MV and 60Co. Using 60Co gamma rays as the standard, the relative biologic effectiveness was as follows: 250 kVp greater than 25 MV greater than 6 MV = 60Co. The data suggest that there may be a greater damage to tissue within the marrow cavities following exposure to very high megavoltage radiation, a factor which must be considered with the increasing utilization of linear accelerators in the clinic and laboratory.

High energy fast neutrons from the Harwell variable energy cyclotron. II. Biologic studies in mammalian systems

A high energy fast neutron beam potentially suitable for radiotherapy has been described in a companion paper. Its biologic effects have been studied in the following experimental systems: clonal survival and mutation induction after irradiation in vitro in Chinese hamster cells and human diploid fibroblasts; survival of reproductive capacity in vivo of murine hemopoietic colony-forming cells and murine intestinal crypts after irradiation in vivo; survival of reproductive capacity in vivo after irradiation in vitro or in vivo of murine lymphocytic leukemia cells; acute intestinal death following total body irradiation of mice and guinea pigs; and hemopoietic death following total body irradiation of mice and guinea pigs. The relative biologic effectiveness of these high energy neutrons varied among the different biologic systems, and in several cases varied with the size of the radiation dose. The oxygen enhancement ratio was studied in murine lymphocytic leukemia cells irradiated under aerobic or hypoxic conditions in vitro and assayed for survival of reproductive capacity in vivo. Compared with x-rays, the potential therapeutic gain factor for these neutrons was about 1.5. This work represents a ''radiobiologic calibration'' program which it is suggested should be undertaken before new and unknown fast neutron spectra are used for experimentalmore » radiotherapy. The results are compared with biologic studies carried out at high energy fast neutron generators in the United States.« less

SURVIVAL TIME IN GERMFREE MICE AFTER LETHAL WHOLE BODY X-IRRADIATION.

The survival time of germfree Swiss-Webster mice to whole-body X-irradia-tion in the range of 500 to 35, 000R was compared to that of conventional Swiss-Webster mice. The relationship between the survival time and X-ray dose administered to germfree and conventional mice shows three different straight line segments and cne curved segment, each with distinctive dose response characteristics on a log-log scale. No essential difference can be recognized on the dose-response rela-tions between germfree and conventional mice. However, the mean survival time of germfree mice in the X-ray dose range which causes “hemopoietic death” is 12.5 days as compared to 11.2 days for conventional mice, a difference of 1.3 days. The mean survival time of germfree mice in the so-called “gut death” range is 7.2 days as compared to 3.4 days of conventional mice, more than twice the difference. In general, the survival time of germfree mice in the zone of death caused by damage to the cell renewal system was much longer than that of conventional mice. However, the survival time of germfree mice in the so-called “brain death” X-ray dose range (over 17, 500R) is reversed and is shorter than that of conventional mice.