光泽汀体内遗传毒性风险评价

目的 评价光泽汀小鼠体内的遗传毒性。方法 C57BL/6J小鼠分为溶剂对照（0.5% CMC-Na）组、茜草素（200 mg·kg^-1,结构对照）组、乙酰基亚硝基脲（ENU,40 mg·kg^-1,阳性对照）组、甲基磺酸乙酯（EMS,200 mg·kg^-1,阳性对照）组和光泽汀低、中、高剂量（100、200、300 mg·kg^-1）组,溶剂、光泽汀和茜草素连续7 d ig给予,给药第1天记为D1,阳性对照ENU和EMS分别连续3 d给予,均每天给药1次。于D7、D56采集约0.5 mL外周血用于血清生化检测;于D14、D28、D42、D56采集外周血开展Pig-a基因突变试验;末次给药后采集肝、肾细胞开展彗星试验,分析每只动物至少100个细胞的尾DNA百分含量;末次给药后制备骨髓细胞样本,计算嗜多染红细胞的微核发生率。解剖后取心、肝、脾、肺以及肾脏进行组织病理学检查。结果 试验期间所有动物一般症状未见明显异常,各组动物体质量未见明显差异,未见与给予受试物有关的组织病理学改变。光泽汀低、中、高剂量组及EMS组肾脏尾DNA百分率均显著高于溶剂对照组（P<0.05、0.001）,光泽汀高剂量组及EMS组肝脏尾DNA百分率与溶剂对照组比较显著增加（P<0.05、0.001）。光泽汀与茜草素的小鼠骨髓微核试验、Pig-a基因突变试验均为阴性。结论 100～300 mg·kg^-1光泽汀未见对小鼠整体产生明显毒性。光泽汀可导致小鼠肝、肾细胞DNA损伤,肾细胞DNA损伤程度更为严重。

Risk assessment of in vivo genotoxicity of lucidin

Objective To evaluate the in vivo genotoxicity risk of lucidin in mice. Methods C57BL/6J mice were divided into solvent control (0.5% CMC-NA) group, alizarin (200 mg·kg^-1, structural control) group, acetyl nitrourea (ENU, 40 mg·kg^-1, positive control) group, ethyl methyl sulfonate (EMS, 200 mg·kg^-1, positive control) group, and lubutin low-dose, medium-dose and highdose (100, 200, 300 mg·kg^-1) groups, the solvent, lubutin and alizarin were given intragaigally for consecutive 7 d, denoted D1 on the first day of administration, and positive control ENU and EMS were given for consecutive 3 d, once a day, respectively. About 0.5 mL of peripheral blood was collected on D7 and D56 for serum biochemical detection; peripheral blood was collected on D14, D28, D42 and D56 after administration for Pig-a gene mutation test; liver and kidney cells were collected after the last administration, and comet assay was perfomed to analyze the percentage of tail DNA in at least 100 cells of each animal. Bone marrow cell samples were prepared after the last administration, and the incidence of micronuclei of polychromatic erythrocytes was calculated. After dissection, the heart, liver, spleen, lung and kidney were taken for histopathological examination. Results During the study period, all animals had no obvious abnormal clinical symptoms, there was no significant difference in the body weight of animals in each group during the test period, and no histopathological changes related to the administration of the test substance were found. The percentages of DNA tails in kidneys in the low, medium, and high-dose groups and EMS groups were significantly higher than those in the vehicle control group, and the changes were statistically different (P<0.05, 0.001). Compared with the vehicle control group, the percentage content increased, and the change was statistically significant (P<0.05, 0.001). Compared with the vehicle control group, there was no significant difference in the percentage of DNA tails in liver and kidney in the alizarin group. The mouse bone marrow micronucleus test of lucidin and alizarin were both negative. There was no significant difference in RBC^CD24- and RET^CD24- and vehicle control groups in each dose group of lucidin and alizarin group. Conclusion There is no obvious overall toxicity of lucidin in mice 100-300 mg·kg^-1. Lucidin causes DNA damage in mouse liver and kidney cells, and the degree of DNA damage in kidney cells is more serious.