John B. Storer

Chemoprotection against Three Modes of Radiation Death in the Mouse

SummarySeven radioprotective agents have been tested for their ability to protect the mouse against three radiation-induced modes of death. Six of the seven agents offer relatively less protection against gastrointestinal death than against haematopoietic death, and only one (PAPP) is effective against CNS death. It is proposed that the variations in protection against the three forms of death may be the result of tissue-specific differences in the ability to concentrate and respond to each agent.

The Effect of Age on Two Modes of Radiation Death and on Hematopoietic Cell Survival in the Mouse

Female C57BL/6J mice, between the ages of 3 and 24 months, have been tested for three measures of radiosensitivity: marrow death, intestinal death, and hematopoietic stem cell content and sur...

Radiation resistance with age in normal and irradiated populations of mice.

These considerations also apply to the problem of estimating residual radiation injury in irradiated populations at long times after the initial exposure. In this context, residual radiation injury refers to that component of irreparable injury that can be detected as an increased sensitivity to the acute lethal effects of further radiation exposure at times beyond the phase of acute injury and recovery after the initial exposure (6-11). The extent of this injury is usually measured by the classical split-dose technique (6). On the basis of the assumptions and definitions utilized in this technique, residual injury usually amounts to about 5 to 10% of the total injury sustained after the initial exposure (90 to 95% of the injury is repaired). It is often assumed that the level of residual injury remains constant throughout the remaining life of the animal, but experimental data are not entirely adequate to support this assumption. The derived impulse lethality function of Sacher and Grahn (12) suggests an ever more slowly decreasing level of injury throughout life after a single exposure. This function is based on data obtained by

Effect of dose size on rate of recovery from radiation damage in mice.

Latent residual injury contributing to the acute lethal response in RF/J mice 80 to 120 days old after x ray doses of 100 to 650 r was estimated at 2 days after exposure by determining the additional dose required to produce 50% mortality in 30 days. The fraction of latent damage repaired, as measured by this technique, decreased progressively with increasing dose. On the assumption that the recovery pattern can be described by a simple exponential equation, recovery nate constants for the various doses were estimated. It was concluded that the recovery rate decreased inversely with the square of the dose, and it was suggested that equations using recovery rate constants should be modified accordingly. When repair was expressed in terms of roentgens of latent damage repaired, it appeared that a maximum rate of repair occurred at a dose of 300 r. Higher doses severely depressed the repair mechanism. (auth)

Rate of Recovery from Radiation Damage and Its Possible Relationship to Life Shortening in Mice

The recovery rate of animals exposed to sublethal doses of radiation and subsequently challenged by a second dose of radiation has been studied in detail by a number of authors (1-10). In these studies, which utilize lethality as the biological end point, it has generally been found that in mice and rats recovery can be described as a simple exponential function. When the recovery rate so determined has been utilized to predict median lethal doses for fractionated exposures extending over several days, however, the observed LD50 has generally been lower than that predicted on the assumption of a constant recovery rate. This finding has led to the suggestion that repeated exposures cause a progressive decline in recovery rate (1, 4, 5), but an analysis of the rate of decline has not as yet been performed. Blair (11-13), utilizing the concept of a constant repair rate for reparable radiation damage and the premise that a portion of the damage does not repair, has advanced an interesting hypothesis that attempts to relate the acute LD50 to mean survival time (life shortening) at very long times after radiation exposures. Since there are now a number of published reports on the survival times of mice exposed to a great variety of daily doses of radiation, it was considered worth while to re-examine these data and to calculate mean recovery rate constants for animals exposed to different numbers of daily radiation doses. If a systematic variation in recovery rate with number of fractions could be demonstrated, it was then planned to modify certain aspects of Blairs hypothesis accordingly and to apply the modified hypothesis to certain cases of experimentally produced life shortening from radiation. These calculations and modifications of the Blair hypothesis are the subject of the present report.

Evaluation of radiation response as an index of aging in mice.

Life table data were obtained on 3904 RF/J female mice. Approximately half the mice received 400 r of x rays at 90 days of age. Gross mortality rates in the irradiated population showed marked departures from the Gompertz equation. Median life span was shortened by 178 days. Correction of mortality rates for leukemia incidence enabled a reasonably good fit of the Gompertz equation to data from both populations. The corrected data indicated a life shortening of 24 days per 100 r of exposure. No latent period between time of exposure and a detectable increase in mortality rate relative to the control rate was found. The mortality rate in the irradiated population was higher at all time intervals after exposure. The LD/sub 50(30)/ was found to decline approximately linearly with age. No pronounced effect of previous exposure was observed. Survival under daily exposure to 100 r/day declined with age in a complex manner. Previously irradiated animals were generally more sensitive than controls. The recovery rate as estimated by split doses declined sharply with age. Recovery rates in previously irradiated mice were considerably lower than those in controls of comparable ages. None of the radiation responses measured showed a consistent relationship tomorexa0» mean life expectancy. It was concluded that radiation exposure does not cause a true, nonspecific, premature aging but selectively damages certain organ systems. (auth)«xa0less

On the Relationship between Genetic and Somatic Sensitivity to Radiation Damage in Inbred Mouse Strains

The incidence of dominant lethal mutations in spermatozoa estimated by postimplantation death in embryos sired by male mice irradiated with 600 R and mated one day later to female mice of the same strain or to C57BL/6J female mice was measured in four strains known to differ in somatic radiation sensitivity. In the inbred embryos (from matings between mice of the same strain) there were significant differences in embryonic mortality with the ordering of sensitivity identical to the ordering of the somatic radiation sensitivity of adults of the same strain. When the embryos were hybrids (from matings to C57BL/6J females) there were no significant differences in mortality. It was concluded that there were no strain differences in the susceptibility to the induction of chromosome damage in spermatozoa, but that radiosensitive strains were more sensitive to the induced damage, and lethality in radiosensitive strains resulted from injury which was sublethal in radioresistant strains.

Relative Effectiveness of Neutrons for Production of Delayed Biological Effects: I. Effect of Single Doses of Thermal Neutrons on Life Span of Mice

White Swiss mice were exposed to single, graded doses of x rays of thermal column radiation (thermal neutrons plus gamma rays) and allowed to live their life span. Mean life span was calculated for each group, and per cent life shortening as a function of dose was determined. Under the conditions of the experiment, life shortening amounted to about 5% per 100 rads for either type of radiation. The relative biological effectiveness (RBE) of thermal column radiation for shortening life span was 1.00 plus or minus 0.24, a value not significantly different from the RBE for the production of 30-day death. (auth)

RESIDUAL RADIATION INJURY: HEMATOPOIETIC AND GASTROINTESTINAL INVOLVEMENT IN RELATION TO AGE.

Residual radiation injury (the depression in resistance to 140 R/day, 5 days a week) owed to 500 R given 30 days earlier has been measured in C57BL/6J female mice between the ages of 3 and 23 month...

Effect of Leukocyte-Promoting Factor (LPF) on Survival of X-Irradiated Mice.

Summary The present study does not contribute to the discussion as to whether or not a “humoral” substance is secreted by the spleen. It does show, however, that LPF, a logical therapeutic agent, is ineffective in reducing X-ray mortality in mice.