抗肿瘤血清胸腺因子9肽的急性毒性和遗传毒性

目的： 观察抗肿瘤创新药血清胸腺因子9肽是否存在急性毒性和遗传毒性，为临床用药提供安全性依据。方法： 小鼠、大鼠和Beagle犬一次性注射给予70.0 mg/kg血清胸腺因子9肽进行急性毒性试验，采用Ames试验、中国仓鼠肺成纤维细胞（CHL）染色体畸变试验和小鼠骨髓细胞微核试验组合进行血清胸腺因子9肽的遗传毒性试验。结果： 一次性注射给药后3种动物精神好、行为正常，均未出现兴奋或抑制体征，均未发现动物急性毒性表现；Ames试验在1~5 000 μg/皿浓度各菌株的平均回变菌落数均与溶剂对照组相似，未见明显增加（P>0.05）；CHL染色体畸变试验在1 400~5 600 μg/mL剂量范围内染色体畸变率均≤3%，与溶剂对照组比较，差异均无统计学意义（P>0.05）；微核试验在17.5~70.0 mg/kg剂量组的微核细胞率均<2.0‰，与溶剂对照组（1.2‰）比较，差异均无统计学意义（P>0.05）。结论： 小鼠、大鼠和Beagle犬对血清胸腺因子9肽的最大耐受剂量>70.0 mg/kg，按体质量计算相当于临床人拟用量的930倍；在本试验剂量范围内未见血清胸腺因子9肽的急性毒性和遗传毒性作用。

Acute toxicity and genotoxicity of antitumor serum thymic factor 9 peptide

OBJECTIVE: To investigate acute toxicity and genotoxicity of an innovative antitumor drug -serum thymus factor 9 peptide. METHODS: Mice,rats,beagles were given 70.0 mg/kg by one-time injection to test for acute toxicity. Ames test,CHL test and micronucleus test were used to investigate genotoxicity. RESULTS: After treatments,the animals were in good spirits and behaved normally. There were no signs of excitation or inhibition. No acute toxicity was found. Ames test showed no significant increase in the number of mutant colonies at 1-5 000 μg/dish,similar to the solvent control group. CHL test showed no significant increase in chromosome aberration rate at 1 400-5 600 μg/mL (less than 3%),there was no statistical significance compared with the solvent control group (P>0.05). The micronucleus cell rates in the 17.5-70.0 mg/kg group were all less than 2.0‰,and there was no statistical significance compared with the solvent control group (1.2‰) (P>0.05). CONCLUSION: The maximum tolerated dose of serum thymic factor 9 peptide was greater than 70.0 mg/kg,which was 930 times of the recommended dosage for clinical patients. Acute toxicity and genotoxicity were not observed in the dose ranges for this investigation.