盐酸苯海拉明咖啡因复方的遗传毒性评价  

Evaluation of genotoxicity of diphenhydramine hydrochloride and caffeine compound

作　　者：侍雯婧 张吉芊竹 朱江波 张晓芳 王瑞娜 戴小宇 任丽君 田逸君 SHI Wenjing;ZHANG Jiqianzhu;ZHU Jiangbo;ZHANG Xiaofang;WANG Ruina;DAI Xiaoyu;REN Lijun;TIAN Yijun(Department of Hygeine and Toxicology,Shanghai 200433;Department of Pharmacy,Naval Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学卫生毒理学教研室,上海200433 [2]海军军医大学药学系,上海200433

出　　处：《癌变．畸变．突变》2022年第2期149-153,157,共6页Carcinogenesis,Teratogenesis & Mutagenesis

摘　　要：目的:研究盐酸苯海拉明咖啡因复方(盐酸苯海拉明/咖啡因质量比为1/2.4)是否具有遗传毒性。方法:采用鼠伤寒沙门氏菌回复突变试验(Ames试验),体外培养中国仓鼠肺(CHL)细胞染色体畸变试验和ICR小鼠骨髓微核试验检测盐酸苯海拉明咖啡因复方的遗传毒性。Ames试验选用TA97、TA98、TA100、TA102及TA1535为指示菌株,设0.5、5、50、500、5000 mg/皿共5个受试剂量组;CHL细胞染色体畸变试验设低、中、高(分别为8.45、16.9、33.8 mg/mL)3个剂量组;小鼠骨髓微核试验采用ICR小鼠经口灌胃的方式一次给予盐酸苯海拉明咖啡因复方,设低、中、高3个剂量组,分别为21.59、43.17和86.35 mg/kg。结果:与对照组相比,Ames试验结果提示在0.5、5、50、500、5000 mg/皿剂量下,在加和不加代谢活化系统S9时对鼠伤寒沙门氏菌均无致突变性(P>0.05)。CHL细胞染色体畸变试验结果提示在终浓度8.45、16.9和33.8 mg/mL剂量组,在加与不加S9代谢活化系统培养CHL细胞24 h和4 h的条件下均未诱发染色体畸变(P>0.05)。小鼠骨髓微核试验在21.59、43.17和86.35 mg/kg剂量下对ICR小鼠诱发的微核率与溶剂对照组比较差异均无统计学意义(P>0.05)。结论:在本实验条件下,盐酸苯海拉明咖啡因复方不具有遗传毒性和潜在致癌性。OBJECTIVE:To investigate genetic toxicity of diphenhydramine hydrochloride and caffeine(mass ratio of diphenhydramine/caffeine is 1/2.4).METHODS:Ames test,chromosomal aberration test in CHL cells and ICR mouse bone marrow micronucleus assay were used to evaluate dphenhydramine hydrochloride and caffeine compound.In Ames test,TA97,TA98,TA100,TA102 and TA1535 were selected as indicator strains,and five test dose groups of 0.5,5,50,500 and 5000 mg/dish were set.Chromosomal aberration test of CHL cells was divided into three dose groups,low dose(8.45 mg/mL),medium dose(16.9 mg/mL)and high dose(33.8 mg/mL).Mouse bone marrow micronucleus assay:ICR mice were given the compounds by oral gavage.There were three dose groups:low dose(21.59 mg/kg),medium dose(43.17 mg/kg)and high dose(86.35 mg/kg).RESULTS:Results of the Ames test show that there was no mutagenicity against Salmonella typhimurium with or without the metabolic activation system(S9).After CHL cells were exposed for 24 h and 4 h with or without S9,no chromosomal aberration effect was observed.In the mouse bone marrow micronucleus assay,the induction rates of micronucleus for the three doses were not significantly different from that of the solvent control group(P>0.05).CONCLUSION:These results indicate that diphenhydramine hydrochloride and caffeine compound had no genotoxicity based on our experimental conditions.

关 键 词：苯海拉明 咖啡因 遗传毒性 AMES试验 染色体畸变试验 微核试验 

分 类 号：Q355[生物学—遗传学]