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

We have investigated the effect of the adaptive response on acute myeloid l eukemia (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 chro nic dose rates (0.5, 0.004 Gy/h) had similar frequencies of AML. Compared t o 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 leu kemia. The survival rates of irradiated mice that did develop leukemia in t he 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 ioni zing radiation, mild hyperthermia (40.5 degrees C whole-body, 60 min) or tr eatment 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 (2 4 h later) 1.0-Gy (0.5 Gy/h) chronic radiation exposure. The frequency of r adiation-induced leukemia was not changed in mice given any of the three ad apting treatments 24 h prior to the chronic 1.0-Gy dose that induced leukem ia. However, the latent period for development of AML was significantly inc reased by both the prior low radiation dose and mild: hyperthermia treatmen t. Injection of interleukin-l, in contrast, may have reduced the latent per iod. Similar to the single 1.0-Gy chronic exposure alone, none of the adapt ing treatments prior to that exposure influenced the survival of animals th at did not develop AML. These results indicate that an earlier exposure ito a small adapting dose of radiation or to a mild heat stress can influence secondary steps in radiation-induced carcinogenesis. (C) 1999 by Radiation Research Society.