消旋酶法DL-丙氨酸的遗传毒性研究

Genotoxicstudy on DL-alanine from racemase

目的评价消旋酶法DL-丙氨酸的遗传毒性。方法小鼠骨髓细胞微核实验设阴性对照组(纯水)、阳性对照组(环磷酰胺40 mg/kg)和消旋酶法DL-丙氨酸3个剂量组(10 000、5 000和2 500 mg/kg),观察各组小鼠胸骨骨髓细胞微核发生率;小鼠精原细胞染色体畸变实验设阴性对照组(纯水)、阳性对照组(环磷酰胺40 mg/kg)和消旋酶法DL-丙氨酸3个剂量组(10 000、5 000和2 500 mg/kg),观察各组小鼠睾丸精原细胞染色体畸变类型并计算畸变率。细菌回复突变实验(Ames实验)设空白对照组、溶剂对照组、阳性对照组和消旋酶法DL-丙氨酸5个剂量组(50、158、500、1 580、5 000μg/皿和8、40、200、1 000、5 000μg/皿),计数各组回复突变菌落数。结果小鼠骨髓细胞微核实验结果显示,各剂量组消旋酶法DL-丙氨酸微核细胞率与对照组的差异无统计学意义(P>0.05);小鼠精原细胞染色体畸变实验结果显示,各剂量组消旋酶法DL-丙氨酸动物睾丸精原细胞染色体畸变率与对照组的差异无统计学意义(P>0.05);细菌回复突变实验结果显示,在加或不加S9的情况下,各剂量组消旋酶法DL-丙氨酸对TA97a、TA98、TA100、TA102、TA1535菌株均无致突变作用,差异无统计学意义(P>0.05)。结论消旋酶法DL-丙氨酸未见明显遗传毒性。

Objective To evaluate the genotoxicity of DL-alanine from racemase. Methods Micronucleus test in mouse bone narrow was used to setnegative control group（ pure water）,positive control group（ 40 mg/kg cyclophosphamide） and three dose levels of DL-alanine from racemase（ 10 000,5 000,2 500 mg/kg）,then the incidence of micronucleus in mouse sternal bone marrow cells in each groupwas observed. Chromosome aberration test of spermatogonia cells in mice was used toset negative control group（ pure water）,positive control group（ 40 mg/kg cyclophosphamide） and three dose levels of DL-alanine from racemase（ 10 000,5 000,2 500 mg/kg）,then the chromosomal aberration types were observed and the aberration rate calculated in each group. The bacterial response mutation test wasused to set blank control group,solvent control group,positive control group and five dose levels of DL-alanine from racemase（ 50,158,500,1 580,5000 μg/plate and 8,40,200,1 000,5 000 μg/plate）,and the number of reversion mutants in each group was counted. Results The micronucleus test of mouse bone narrow and chromosome aberration test of spermatogonial cells in mice showed that each dose DL-alanine from racemase had no difference in chromosome aberration rate and micronucleus rate（ P〈0. 05）. The bacterial response mutation test indicated that none of the bacterial strains tested（ TA97 a,TA98,TA100,TA102,TA1535） showed an increase in revertants with or without S9 mixture at any dose. Conclusion DL-alanine from racemase shows no obvious genotoxicity.