Array-CGH analyses of murine malignant lymphomas. Effects of chronic exposure to low-dose-rate gamma-rays on lymphomagenesis

We previously reported that mice that had been chronically irradiated with low-dose-rate gamma-rays had significantly shorter mean life spans than non-irradiated controls. This life-shortening appeared to be primarily attributable to the earlier death of malignant lymphomas in the irradiated groups. To elucidate the molecular pathogenesis of murine lymphomas under effects of low-dose-rate irradiation, chromosomal aberrations in malignant lymphomas from mice irradiated with gamma-ray at a dose rate of 21 mGy/22 hours/day were compared precisely not only with those from non-irradiated mice, but also with aberrations in thymic lymphomas induced by whole body acute X-irradiation once a week for four consecutive weeks by microarray-based comparative genomic hybridization (array-CGH) analysis. The array carried 667 BAC clones that were densely selected for genomic regions not only of lymphoma-related loci but also of surface antigen receptors, enabling immunogenotyping. Immunogenotyping by array-CGH suggested that most lymphomas from mice irradiated with a low-dose-rate gamma-ray and non-irradiated mice were of B-cell origin, while those induced by acute X-irradiation were of T-cell origin. Array-CGH profiles showed many copy-number imbalances of whole and partial chromosomal regions. Some of these imbalances were associated significantly either with two groups of lymphomas from mice exposed to chronic gamma-ray or acute X-rays. These findings suggest that lymphomagenesis under effects of continuous low-dose-rate irradiation is accelerated by a mechanism that is different both from spontaneous lymphomagenesis and that triggered by acute X-irradiation. (author)