Combination effects of chronic cadmium exposure and gamma-irradiation on the genotoxicity and cytotoxicity of peripheral blood lymphocytes and bone marrow cells in rats

This work investigated the effects of chronic cadmium (Cd) exposure combined with γ-ray irradiation on the cytotoxicity and genotoxicity of peripheral blood cells and bone marrow cells in rats. Results showed that when the rats were exposed to low dose (LD) Cd of 0.1 mg CdCl2/(kg d) for 8 and 12 weeks, the Cd concentration in blood reached to 135–140 μg/L and no toxic effects on peripheral blood lymphocytes, white blood cells (WBC) and granulocyte–monocyte (GM) progenitor cells were observed except polychromatic erythrocytes (PCE) of bone marrow. Moreover, this chronic LD Cd exposure significantly decreased irradiation-induced micronucleus (MN) formation and hypoxanthine–guanine phosphoribosyl transferase (hprt) mutation in lymphocytes and PCE, while the combination of LD Cd exposure and irradiation induced the additive metallothionein (MT) protein expression in bone marrow cells. When the rats were exposed to a high dose (HD) Cd of 0.5 mg CdCl2/(kg d) for 8 and 12 weeks, the blood Cd level approached to 458–613 μg/L and an inflammatory response was induced, meanwhile, MN formation and hprt mutation were markedly increased, and the ratio of PCE/NCE (normochromatic erythrocyte) was significantly decreased. Furthermore, when the rats were exposed to HD Cd plus 2 Gy irradiation, additive toxic effects on MN formation, hprt mutation, PCE damage and GM progenitor cell proliferation were observed, while this combination treatment resulted in an obvious reduction of MT protein compared to HD Cd group. In conclusion, chronic exposure to LD Cd induced the adaptive response to irradiation in the genotoxicity of peripheral blood lymphocytes and PCE of bone marrow by the up-regulation of Cd-induced MT protein, but the combination of HD Cd exposure and irradiation generated the additive effects on the cytotoxicity and genotoxicity in peripheral blood lymphocytes and bone marrow cells.

► The effects of chronic Cd exposure combined with IR on hematological system in rats.
► Exposure to low dose Cd induces the adaptive response to IR in the genotoxicity.
► The combined high dose Cd exposure and IR produce synergistic cytotoxic and genotoxic effects.
► Rats exposed to high dose Cd show inflammatory response with the increased amount of WBC.
► Polychromatic erythrocytes of bone marrow were more sensitive to Cd exposure than peripheral lymphocytes and granulocyte–monocyte progenitor cells.