使用体内多终点遗传毒性检测体系评估2-甲基呋喃的遗传毒性

Assessment of the genotoxicity of 2-methylfuran based on a multi-endpoint genotoxicity test system in vivo

目的使用体内遗传毒性综合评价体系(Pig-a基因突变试验、流式微核试验和彗星试验)检测2-甲基呋喃的体内遗传毒性。方法 30只SPF级雄性SD大鼠分为6组,染毒组连续3 d经口灌胃染毒2-甲基呋喃25、50、100和150 mg/kg,溶剂对照为植物油,阳性对照为80 mg/kg N-乙基-N-亚硝基脲。于试验第3 d给药后3 h进行外周血彗星试验;试验第0(灌胃前1日)、14和28 d进行Pig-a基因突变试验;试验第0、4 d进行外周血微核试验。结果彗星试验中150 mg/kg组彗尾DNA百分含量显著升高;Pig-a基因突变试验结果显示,第14、28 d所有染毒组成熟红细胞和网织红细胞突变率均未见显著升高;流式微核试验所有染毒组网织红细胞微核率未见显著升高。结论该实验条件下,2-甲基呋喃急性暴露具有诱变性的可能性较低。

OBJECTIVE This study was designed to determine the genotoxicity of 2-methylfuran based on a multi-endpoint genotoxicity test system. METHODS The SPF-grade male SD rats(n = 30) were randomized to six treatment groups,i. e. 4 treatment groups(25,50,100 and 150 mg/kg),a control group(vegetable oil) and a positive groups(N-ethyl-N-nitrosourea,80 mg/kg). All treatments were administrated by gavage for continuous 3 days. Tail vein blood for comet assay was collected at 3 h after the final administration. Pig-a gene mutation assays were performed on days 0(one day before gavage),14 and 28. Micronucleus tests in peripheral blood using flow cytometry were performed on days 0 and 4. RESULTS A statistically significant increase in tail intensity was observed at 150 mg/kg for peripheral blood in comet assay. There was no significant difference among the groups in mutant cell frequency of erythrocytes and reticulocytes at 2 timepoints in Pig-a gene mutation assay,and no significant difference among the groups in the frequency of micronucleus in micronucleus test. CONCLUSION The result of genotoxicity tests suggested that 2-methylfuran was probably not mutagenic in vivo after acute exposure.