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目的探讨酚噻嗪类光敏剂YWW007应用于血液病原体灭活的安全使用剂量。方法细胞毒性试验:使用YWW007终浓度为1、4、12、20、40μmol/L培养基培养小鼠成纤维细胞,用四甲基偶氮唑盐比色(MTT)方法检测细胞存活率;遗传毒性评价:采用YWW007终浓度为1、2、4、6、8、12μmol/L的培养基培养小鼠淋巴瘤细胞,用微孔板法做tk基因突变试验,计算平板效率、相对存活率以及TFT抗性突变频率等指标。结果当YWW007浓度达到40μmol/L时,具有明显的细胞毒性;而YWW007浓度为12、4、2和1μmol/L时,细胞存活率>70%,提示细胞毒性轻微;YWW007浓度≤4μmol/L时,在含有和不含有代谢活化系统(S9)条件下,其突变频率(MF)值均未达到阴性对照组MF值的2倍,未见剂量-效应关系。结论 YWW007浓度≤4μmol/L为用于病原体灭活的安全剂量。
Objective To investigate the safe dosage of phenothiazine photosensitizer YWW007 for inactivation of blood pathogens. Methods Cytotoxicity test: Mouse fibroblasts were cultured with YWW007 at the final concentration of 1, 4, 12, 20, 40 micromol / L and cell viability was measured by MTT assay. Toxicity evaluation: Mouse lymphoma cells were cultured with YWW007 at the final concentration of 1, 2, 4, 6, 8, 12 μmol / L, and the tk gene mutation test was performed by the microplate method to calculate the plate efficiency, relative survival rate and TFT resistance mutation frequency and other indicators. Results When YWW007 concentration was 40μmol / L, cytotoxicity was obvious. When YWW007 was at concentrations of 12, 4, 2 and 1μmol / L, the cell viability was over 70%, indicating slight cytotoxicity. When YWW007 concentration was below 4μmol / L , The mutation frequency (MF) did not reach 2 times MF value of negative control group with or without metabolic activation system (S9), and no dose-effect relationship was found. Conclusion YWW007 concentration ≤4μmol / L is a safe dose for pathogen inactivation.