Combined Effects Of γ-irradiation And Cadmium Exposure On Bone

With the rapid development of industry and nuclear technology, environmental pollution has appeared worldwide, such as heavy metals, polycyclic aromatic hydrocarbons and radioactive pollution. And these pollutions appeared not only in occupational exposure populations, but also could get into human body through food chain. Effects of environmental factors to bone were rarely concerned previously. However, environmental factors especially heavy metals including nonradioactive heavy metals (cadmium and lead) and radioactive heavy metals (uranium, strontium-90) pollution once got into body, they would accumulate in kidney and bone, and possibly through direct action on bone, or through kidney-skeletal indirect-effect, cause bone damage. The United States, the EU and developing countries have paid wide attention to this problem. However, it is difficult to evaluate the combined biological effects of variety of environmental pollution factors existing the same time, and there is no corresponding evaluation standard as far. At present, we have paid wide attention to the renal bone effects induced by environmental cadmium(Cd) pollution. And osteoradionecrosis is a complication of radiation therapy for cancer because of high dose irradiation. However, combined effects of Cd and ionizing radiation on bone metabolism and bone mineral are rarely studied. In our study, we investigated combined effects of Cd and y-irradiation on bone in pathophysiological characteristics and related mechanism of action.,In order to determine the specific actions of manifold environmental pollutants on bone, we investigated the combined effects of Cd and y-irradiation on bone and related mechanisms from animal and cell experiments in this study, to provide a theoretical basis to evaluate Cd combined with ionizing radiation on human health hazards. For animal studies, animals in all groups were received subcutaneous injection of CdCl2, and exposed to γ-irradiation. Bone mass, bone biomechanics, bone morphology and bone metabolic markers were observed. And combined effects of Cd and y-irradiation on kidney were also observed to discuss the role of kidney in bone effects. In vitro study, combined effects of Cd and γ-irradiation on osteoblasts and osteoclasts were observed. Related genes expression of osteoblasts was also tested to investigate the mechanism for the combined effects of Cd and γ-irradiation on bone effects. In animal study, a linear relationship was observed between BCd and Cd concentrations. BCd can reflect the changes of Cd concentrations. Gamma ray single irradiation did not change the trend of BCd. With increasing Cd concentration, Cd accumulated in bone tissue linearly rose. Gamma ray irradiation did not change the trend of Cd in bone tissue after treatment with low and medium concentrations of Cd, but gamma ray irradiation enhanced accumulation level of high concentration of Cd in bone. Lumbar BMD (bone mineral density) or rats was decreased within12weeks Cd ingestion, especially medium and high concentrations of Cd decreased BMD significantly (p<0.01). And2Gy γ-irradiation did not enhance the effect of Cd to BMD. Bone biomechanical indexes (elastic module, compression, yield strength and bending load of lumbar, load, strain, crack energy and stiffness of femur) were decreased after treatment with Cd. And in combination with y-irradiation, high concentration of Cd induced more significant decrease to some certain extent in above bone biomechanical indexes than Cd alone. Lumbar mechanical indexes are more sensitive to Cd in combination with y-irradiation exposure than femur mechanical indexes. Bone formation function indexes were found to be inhibited (ALP in blood and OC in blood were decreased with Cd exposure) by Cd. Bone resorption function indexes were found to be increased (Tracp-5b in blood was increased with Cd exposure) by Cd. Cd combined with y-irradiation exposure induced combined action to bone metabolism function, and appeared earlier than the impacts to BMD and bone mechanical properties. High concentration of Cd exposure and high concentration of Cd combined with y-irradiation exposure could increase the levels of urinaiy total protein and UNAG of rats significantly. In combination with y-irradiation, Cd exposure resulted in larger increase in urinary total protein and UNAG compared with those treated with Cd alone. And vacuolization and necrosis of renal tubular cells were observed after treatment with Cd or Cd+γ-irradiation exposure. In combination with y-irradiation, renal tubular of rats in Cd+γ-irradiation exposure group were damaged more significantly than Cd exposure group. In conclusion, bone mass, bone mechanical properties, bone morphology, bone metabolism and kidney were damaged by Cd exposure. Cd combined with ionizing radiation exposure could induce synergistic effects to some certain extent to bone mass, bone mechanical properties, bone morphology and bone metabolism. Cd could impact function of kidney, and ionizing radiation could enhance damage levels of Cd to kidney. And the injury of kidney can affect bone function and metabolism. The impact of Cd+γ-irradiation to kidney may play important roles in the synergistic effects of Cd and ionizing radiation to bone. In addition, enhancement accumulating level of Cd in bone after exposure to Cd combined with y-irradiation may be one reason for enhancement of bone damage.In vitro study, low concentration of Cd exposure had no obvious influence on cell viability, ALP activity and apoptosis. However, low concentration of Cd combined with γ-radiation exposure reduced cell viability, ALP activity and induced apoptosis on osteoblasts. Medium and high concentrations of Cd combined with irradiation exposure induced more significant inhibition in cell viability, ALP activity and mineralization ability than those exposed to Cd alone. Meanwhile, OC and ALP mRNA expression of cells treated with Cd combined with irradiation were down-regulated more significantly than those treated with Cd alone. Cd combined with y-irradiation could obviously enhance osteoblast apoptosis and up-regulated caspase3mRNA expression compared with those treated with Cd alone. So ionizing irradiation combined with cadmium exposure could enhance the effects of cadmium on osteoblasts. The number of TRACP (+) osteoclasts induced by RANKL was increased significantly by Cd, and Cd combined with irradiation exposure induced more significant rise in number of TRACP (+) osteoclasts than those exposed to Cd alone.In conclusion, it was suggested that Cd and gamma ray could decrease bone mass and bone biomechanics, change bone morphology, inhibit bone formation and enhance bone resorption. Cd combined with y-irradiation exposure could damage bone synergistically to certain extent, enhancing accumulating level of Cd in target organ (bone), affecting bone mass, bone biomechanics, bone morphology and bone metabolism, and inducing kidney dysfunction. Further vitro study proved that Cd and ionizing radiation exposure could affect osteoblasts directly, inducing cell apoptosis ability, inhibiting bone formation of osteoblasts, enhancing ability of osteoclasts. And combined exposure of Cd and γ-irradiation also show a synergistic impact to bone. And this result may be one important mechanism for the synergistic damage to bone after exposure with Cd and γ-irradiation.