[關(guān)鍵詞]
[摘要]
目的 評(píng)價(jià)光澤汀小鼠體內(nèi)的遺傳毒性。方法 C57BL/6J小鼠分為溶劑對(duì)照(0.5% CMC-Na)組、茜草素(200 mg·kg-1,結(jié)構(gòu)對(duì)照)組、乙?;鶃喯趸澹‥NU,40 mg·kg-1,陽(yáng)性對(duì)照)組、甲基磺酸乙酯(EMS,200 mg·kg-1,陽(yáng)性對(duì)照)組和光澤汀低、中、高劑量(100、200、300 mg·kg-1)組,溶劑、光澤汀和茜草素連續(xù)7 d ig給予,給藥第1天記為D1,陽(yáng)性對(duì)照ENU和EMS分別連續(xù)3 d給予,均每天給藥1次。于D7、D56采集約0.5 mL外周血用于血清生化檢測(cè);于D14、D28、D42、D56采集外周血開展Pig-a基因突變?cè)囼?yàn);末次給藥后采集肝、腎細(xì)胞開展彗星試驗(yàn),分析每只動(dòng)物至少100個(gè)細(xì)胞的尾DNA百分含量;末次給藥后制備骨髓細(xì)胞樣本,計(jì)算嗜多染紅細(xì)胞的微核發(fā)生率。解剖后取心、肝、脾、肺以及腎臟進(jìn)行組織病理學(xué)檢查。結(jié)果 試驗(yàn)期間所有動(dòng)物一般癥狀未見明顯異常,各組動(dòng)物體質(zhì)量未見明顯差異,未見與給予受試物有關(guān)的組織病理學(xué)改變。光澤汀低、中、高劑量組及EMS組腎臟尾DNA百分率均顯著高于溶劑對(duì)照組(P<0.05、0.001),光澤汀高劑量組及EMS組肝臟尾DNA百分率與溶劑對(duì)照組比較顯著增加(P<0.05、0.001)。光澤汀與茜草素的小鼠骨髓微核試驗(yàn)、Pig-a基因突變?cè)囼?yàn)均為陰性。結(jié)論 100~300 mg·kg-1光澤汀未見對(duì)小鼠整體產(chǎn)生明顯毒性。光澤汀可導(dǎo)致小鼠肝、腎細(xì)胞DNA損傷,腎細(xì)胞DNA損傷程度更為嚴(yán)重。
[Key word]
[Abstract]
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 RBCCD24- and RETCD24- 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.
[中圖分類號(hào)]
R994
[基金項(xiàng)目]
國(guó)家自然科學(xué)基金資助項(xiàng)目(81503347);國(guó)家十三五"重大新藥創(chuàng)制"專項(xiàng)(2018ZX09201017)