Nutrition status and radiation-induced cancer in mice

Dietary restriction, especially caloric restriction (CR), is a major carcinogenic modifier during experimental carcinogenesis. We attempted to examine the effects of CR on radiation-induced myeloid leukemia (MyL). The spontaneous incidence of MyL in C3H/He mice is 1.1%, and the incidence increases to 21.6% by X-ray irradiation. However, the incidence was decreased in the CR groups; it was 7.9% in RA (life-span restricted diet from the age of 6 weeks), 10.7% in RB (restricted diet after irradiation), 16.2% in RC (restricted from 6weeks old until irradiation at 10 weeks old). The differences between both the RA and RB groups and the non-restricted group were statistically significant. The significantly fewer hematopoietic stem cells (HSC), potential target cells for radiation leukemia in the RA and RC at the time of radiation exposure, and the smaller cycling fraction of HSC under CR in the femur of restricted mice (26+-4.5%) than in the non-restricted group (44+-20%), were responsible for this underlying mechanism. CR contributes to the incidence reduction of leukemia at the initiation stage of leukemogenesis and, more significantly, to the reduction of MyL during the promotion stage of radiation leukemogenesis

Stem-cell leukemia: p53 deficiency mediated suppresion of leukemic differentiation in C3H/He myeloid leukemia

C3H/He mice produce myeloid leukemias after whole body irradiation of 1-3Gy as compared with non-irradiated controls that produce fewer than 1% of leukemia [Radiation Research 127 (1991) 146]. Thus, p53-deficient C57BL/6 strain, a malignant lymphoma prone, was crossed back into C3H/He strain. Lethally irradiated wild-type mice to which p53-deficient bone marrow cells were transplanted (transplantation assay) showed dramatic change in the propensity of leukemia of myeloid lineages, the cells lacking CD3, Thy1.2, sIgM, B220, Mac-1, Gr-1, but being positive for c-Kit and CD44. Furthermore, transplanted mice subjected to 3Gy irradiation gave rise to a faster development of leukemia and a higher frequency of double-lineage leukemias than the non-irradiated control

PCA enables identifying characteristic components for experimental spontaneous myeloid Leukemias

9th ICEM Satellite Meeting on Toxicogenomic