OBJECTIVE To detect the genotoxicity of realgar by using short-term administration (mouse bone marrow cell micronucleus test and comet assay) and long-term administration (rat bone marrow cell micronucleus test and comet assay in which bio-samples were collected from reproductive toxicity test) , and to study the possibility of detecting genotoxicity of realgar integrated with reproductive toxicity test. METHODS Mice were ig administered with realgar suspension 0. 25 , 0.5, and 1.0 g·kg-1 for 2 d, before being sacrificed. Bone marrow cells were collected for micro-nucleus tests and comet assay. During early embryonic development, rats were ig given realgar 0. 125, 0.25 and0.55 g·kg-1. The administration lasted at least 42 d for male rats and 19 d for females before they were allowed to mate. After mating successfully, the male rats were sacrificed the next day and the female rats on the 15th day of pregnancy. Then the bone marrow cells and peripheral blood lymphocytes were collected for micronucleus tests and comet assay. RESULTS Compared with negative control group, the micronucleus rate in bone marrow cells with realgar 0. 25 , 0.5 and 1.0 g·kg-1 groups was 3.00‰, 4. 40‰ and 7.01‰, respectively. The tailing rate was 6.3% , 9.7% and 11.3% , respectively(P＜0. 05 , P＜0. 01). In reproductive toxicity rats, the micronucleus rate and lymphocyte micronucleus rate in peripheral blood of male rats with realgar 0.55 g·kg-1 group were 2. 83‰ and 6. 67‰ while those of female rats with realgar 0. 25 and 0.55 g·kg-1 groups were 1.5‰ and 2.25‰, 2. 58‰ and 4.40‰, respectively. The comet tailing rate in realgar 0.125, 0.25 and 0.55 g·kg-1 group had significant differences (P ＜0. 05). CONCLUSION It is feasible to integrate the in vivo micronucleus test and comet assay into reproductive toxicity tests. Micronucleus tests in peripheral blood lymphocytes are simple. Realgar has genotoxicity at the designed doses.%目的 用短期给药(小鼠骨髓细胞微核试验和彗星试验)和长期给药(利用生殖毒性Ⅰ段试验的大鼠做微核试验和彗星试验)检测雄黄的遗传毒性,探讨利用长期毒性试验或生殖毒性Ⅰ段试验用动物进行遗传毒性检测的可行性.方法 小鼠ig给予雄黄0.25,0.5和1.0 g·kg-1,每天1次,2d后,取骨髓细胞做微核试验和彗星试验；利用生殖毒性Ⅰ段大鼠ig给予0.125,0.25和0.55 g·kg-1,雄性连续给药42 d以上,交配成功后处死；雌性连续ig给药19 d以上,妊娠第15天,取骨髓细胞做微核试验和彗星试验,取血做外周血淋巴细胞微核试验.结果 与阴性对照组比较,小鼠雄黄0.25,0.5和1.0g·kg-1组微核试验微核率分别为3.0‰,4.40‰,7.01‰(P＜0.05,P＜0.01)和彗星试验拖尾率分别为6.3％,9.7％和11.3％(P ＜0.05,P＜0.01).与阴性对照组比较,生殖毒性Ⅰ段试验大鼠ig给予雄黄,雄黄0.55 g·kg-1组雄性大鼠的骨髓微核和外周血淋巴细胞微核率分别为2.83‰和6.67‰(P ＜0.05),雌性大鼠0.25和0.55 g·kg-1的骨髓微核和外周血淋巴细胞微核率分别为1.5‰,2.25‰以及2.58‰和4.40‰(P＜0.05,P＜0.01)；雄黄使雄性和雌性大鼠彗星拖尾率明显升高(P ＜0.05).结论 利用生殖毒性Ⅰ段试验多次给药后取材做微核试验和彗星试验方法可行；外周血微核试验简便易行；在所观察的剂量下雄黄具有遗传毒性.
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