慢性镉染毒及联合辐射对大鼠的基因毒性作用

目的 探讨慢性镉染毒及联合辐射对大鼠的基因毒性.方法 雄性SD大鼠分设空白对照组、0.1 mg CdCl2·kg-1·d-1低剂量镉染毒组、0.5 mg CdCl2·kg-1·d-1高剂量镉染毒组、单纯照射组、低剂量镉染毒+照射组和高剂量镉染毒+照射组.腹腔注射镉染毒连续8周,1次/d,然后给予2 Gy γ照射.于照射后第10天或受照即日后继续染镉4周,心脏取血,采用多核细胞法检测外周血淋巴细胞微核率和hprt基因突变率,同时检测外周血白细胞数量变化和血镉含量.结果 大鼠低剂量镉染毒8周和12周组未观察到外周血细胞损伤,而辐射诱导的微核率(F=26.74,P<0.01和F=14.13,P＜0.05)和hprt基因突变率(F=6.60,P＜0.05)显著降低;高剂量镉染毒8周和12周组与空白对照组比较,外周血白细胞数显著增高(F=8.74,P＜0.01和F=13.11,P=0.000),淋巴细胞微核率(F=26.74,P＜0.05和F=14.13,P=0.000)和hprt基因突变率(F=6.60,P＜0.05和F=12.83,P＜0.05)明显增加,而高剂量镉染毒+照射组的基因毒性又显著高于单纯高剂量镉染毒组或单纯照射组,表现出联合毒性效应.结论 慢性、低剂量镉染毒诱导外周血淋巴细胞对辐射产生适应性效应,血镉浓度增加到613～678 μg/L时能刺激白细胞显著增加并与辐射联合作用加重对淋巴细胞的基因毒性.

Abstract：

objective To investigate the effects of chronic cadmium exposure and cadmium exposure combined with γ-ray irradiation on the peripheral lymphocytes and their genotoxicity on hprt gene.Methods Ninety-six SD rats were randomly divided into 6 equal groups:①normal control group,②lowdose cadmium exposure group undergoing intraperitoneal injection of 0.1 mg CdCl2·kg-1·d-1 for 8 weeks,③high-dose cadmium exposure group undergoing intraperitoneal injection of 0.5 mg CdCl2·kg-1·d-1 for 8 weeks,④pure irradiation group exposed to whole-body γ-ray irradiation at the dose of 2 Gy for one time,⑤low-dose cadmium exposure combined with irradiation group undergoing intraperitoneal injection of 0.1 mg CdCl2·kg-1·d-1 for 8 weeks and then whole-body 2 Gy γ-ray irradiation,and ⑥high-dose cadmium exposure combined with whole-body 2 Gy γ-ray irradiation group undergoing intraperitoneal injection of 0.5 mg CdCl2·kg-1·d-1 for 8 weeks and then whole-body 2 Gy γ-ray irradiation.Ten days after the irradiation cardiac blood samples were collected from some of the rats to culture the peripheral lymphocytes to detect the micronucleus rate and hprt mutant frequency of lymphocytes bv multinucleated cell assay.The other rats underwent continuous Cd exposure for 4 weeks after γ-ray irradiation and then cardiac blood samples were collected to detect the micronucleus rate and hprt mutant frequencv of lymphocytes.Meanwhile,the amount of white blood cells(WBC)was counted and the blood cadmium concentration was measured by ICP-MS.Results The numbers of WBC in the peripheral blood at different time points of the high dose cadmium group were significantly higher than those of the normal control group(F=8.74.P<0.01 and F=13.11,P=0.000).The micronucleus rate at difierent time points of the pure irradiation group were significantly higher than those of the control group( F = 26. 74 ,P =0. 000 and F = 14. 13, P = 0. 000). The micronucleus rates of the high-dose cadmium group were significantly higher than those of the control group( F = 26. 74 ,P <0. 05 and F = 14. 13 ,P = 0. 000 ). The micronucleus rates of the low-dose cadmium + irradiation group were significantly lower than those of the pure irradiation group( F = 26. 74, P < 0. 01 and F = 14. 13, P < 0. 05 ). The micronucleus rates of the highdose cadmium + irradiation group were significantly higher than those of the pure irradiation group ( F =26.74,P =0. 000 and F = 14. 13 ,P =0. 000). The hprt mutation rates at different time points of the pure irradiation group were significantly higher than those of the normal control group( F = 6.60, P < 0. 01 and F = 12.83 ,P = 0. 001 ). The hprt mutation rates of the high-dose cadmium group were significantly higher than those of the control group ( F = 6. 60, P < 0. 05 and F = 12.83, P < 0.05 ), but not significantly different from those of the pure irradiation group. However, the hprt mutation rates of the high-dose cadmium + irradiation group were significantly higher than those of the pure irradiation ( F = 12. 83, P =0. 000) and high-dose cadmium group( F = 6.60,P < 0.05 and F = 12. 83, P < 0.05 ). The hprt mutation rates of the low-dose cadmium + irradiation group were significantly lower than those of the pure irradiation ( F = 6. 60, P < 0. 05 ) , but not significantly different from those of the control group. Conclusions Chronic exposure to low dose cadmium induces the adaptive response of lymphocytes to radiation. The cadmium in blood at the level of 613-678 μg/L induces leukocytosis and chronic exposure to high dose cadmium combined with irradiation leads to increased genotoxicity of lymphocytes.