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目的观察不同剂量三氧化二砷(As2O3)对成年大鼠生精细胞DNA损伤及其X射线修复交叉互补基因1(XRCC1)基因表达影响。方法 40只健康雄性SD大鼠随机分为4组,对照组、低、中、高剂量As2O3组(0.375、0.75、1.5 mg/kg),灌胃法连续给药16周处死大鼠,应用单细胞凝胶电泳试验检测大鼠生精细胞DNA损伤,免疫组化法检测大鼠生精细胞XRCC1蛋白表达。结果对照组生精细胞平均尾长(1.04±0.61)μm,中、高剂量As2O3组可见部分细胞拖尾,平均尾长分别为(3.11±1.16)、(3.62±2.46)μm,明显长于对照组(P<0.01),细胞尾部DNA含量比及尾矩也明显增加(P<0.01);中、高剂量As2O3组XRCC1阳性细胞百分比分别为(11.13±7.06)%和(9.63±6.32)%,均较对照组的(15.49±8.23)%明显降低(P<0.05),XRCC1表达量随着染毒剂量增高而降低;DNA损伤与XRCC1表达呈负相关(r=-0.778,P<0.01)。结论一定剂量As2O3可通过抑制生精细胞XRCC1表达,诱导大鼠生精细胞DNA损伤,产生雄性生殖毒性。
Objective To observe the effects of different doses of arsenic trioxide (As2O3) on the DNA damage of adult rat spermatogenic cells and the gene expression of XRCC1. Methods Forty healthy male Sprague-Dawley rats were randomly divided into four groups: control group, low, medium and high dose As2O3 group (0.375,0.75,1.5 mg / kg). Rats were sacrificed by gavage for 16 weeks. The DNA damage of rat spermatogenic cells was detected by cell gel electrophoresis and the expression of XRCC1 protein in rat spermatogenic cells was detected by immunohistochemistry. Results The average tail length of the spermatogenic cells in the control group was (1.04 ± 0.61) μm, and the tail length was (3.11 ± 1.16) and (3.62 ± 2.46) μm in medium and high dose As2O3 groups, which was significantly longer than that in the control group (P <0.01). The content of tail DNA and the content of tail DNA also increased significantly (P <0.01). The percentage of XRCC1 positive cells in medium and high dose As2O3 group were (11.13 ± 7.06)% and (9.63 ± 6.32)% (15.49 ± 8.23)% (P <0.05). The expression of XRCC1 decreased with the increase of exposure dose. The DNA damage was negatively correlated with the expression of XRCC1 (r = -0.778, P <0.01). Conclusion As2O3 can inhibit DNA damage of spermatogenic cells and inhibit male reproductive toxicity by suppressing the expression of XRCC1 in spermatogenic cells.