We have investigated the effect of the adaptive response on acute myeloid leukemia (AML) induced in CBA/Harwell mice by a chronic radiation exposure. Groups of mice irradiated with a total dose of 1.0 Gy at two different chronic dose rates (0.5, 0.004 Gy/h) had similar frequencies of AML. Compared to control animals that did not develop AML, irradiation at either of these dose rates did not change the longevity of the mice that did not die of leukemia. The survival rates of irradiated mice that did develop leukemia in the two groups were not different from each other, indicating that the dose rates produced similar responses and therefore were both chronic exposures. We then tested the ability of a chronic 10-cGy (0.5 Gy/h) exposure to ionizing radiation, mild hyperthermia (40.5°C whole-body, 60 min) or treatment with interleukin-1 (1500 U i.p.) to induce an adaptive response and modify the frequency or latency of AML which resulted from a subsequent (24 h later) 1.0-Gy (0.5 Gy/h) chronic radiation exposu...

The adaptive response modifies latency for radiation-induced myeloid leukemia in CBA/H mice.

Influence of Dose and Its Distribution in Time on Dose-Response Relationships for Low–LET Radiations

Tritium ((3)H) is a radioactive isotope of hydrogen. A number of factors combine to create a good deal of interest in tritium doses, both to workers and to members of the public. Tritium is ubiquitous in environmental and biological systems and is very mobile due to its occurrence as water. In this study we systematically review experimental data relating to tritium exposure with a view to assessing its low dose limiting relative biological effectiveness (RBE(max)). Interpretation of published experimental studies is complicated by the fact that the reference radiations varied, and doses and dose rates were frequently much higher than those normally received by humans. The four available animal carcinogenicity studies gave RBE values of about 2.5 with chronically-delivered gamma-ray reference, and about 1.2 with chronically-delivered X-ray reference. However, because of problems associated with the design and interpretation of the experiments, we do not consider that these RBE values should be taken to apply to the induction of cancer at low doses (i.e. they should not be interpreted as RBE(max)). Combining the six studies with chronic gamma-ray reference, with adequate quantitative data that examined endpoints apart from cell survival and related endpoints, yields an aggregate RBE estimate of 2.19 (95% CI 2.04, 2.33); the analogous combined RBE estimate using the three studies with chronic X-ray reference groups is 1.17 (95% CI 0.96, 1.39). Again, problems with the design, in particular the range of doses used in some of these studies, mean that these RBE values should also probably not be interpreted as RBE(max).

Systematic review of experimental studies on the relative biological effectiveness of tritium.

A dose per unit concentration database has been generated for application to ecosystem assessments within the FASSET framework. Organisms are represented by ellipsoids of appropriate dimensions, and the proportion of radiation absorbed within the organisms is calculated using a numerical method implemented in a series of spreadsheet-based programs. Energy-dependent absorbed fraction functions have been derived for calculating the total dose per unit concentration of radionuclides present in biota or in the media they inhabit. All radionuclides and reference organism dimensions defined within FASSET for marine and freshwater ecosystems are included. The methodology has been validated against more complex dosimetric models and compared with human dosimetry based on ICRP 72. Ecosystem assessments for aquatic biota within the FASSET framework can now be performed simply, once radionuclide concentrations in target organisms are known, either directly or indirectly by deduction from radionuclide concentrations in the surrounding medium.

A method for calculation of dose per unit concentration values for aquatic biota.

The objectives of this review are to: (a) demonstrate that the male CBA/Ca mouse has several characteristics that make it an excellent animal for the study of leukemogenesis, (b) show that several of the genetic abnormalities observed in the male CBA/Ca mouse during the development of radiation induced acute myeloid leukemia (AML) are syntenic with those frequently detected in patients with myeloid disorders such as myelodysplastic syndrome and AML, (c) illustrate that leukemia-related chromosomal lesions are the indicators for high risk individuals.

Advantages of the CBA mouse in leukemogenesis research.

To help resolve uncertainties as to the most appropriate weighting factor for tritium beta rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium beta rays compared to X rays ranged from 1.0 +/- 0.5 to 1.3 +/- 0.3. A best estimate of the RBE for this experiment was about 1.2 +/- 0.3. A wR value of 1 would thus appear to be more appropriate than a wR of 2 for tritium beta rays.

D. H. Percy

Papers

Relative Biological Effectiveness of Tritium for Induction of Myeloid Leukemia in CBA/H Mice