目的 使用基于鼠傷寒沙門氏菌的Ames波動(dòng)試驗(yàn)和小鼠淋巴瘤細(xì)胞（L5178Y）的體外Pig-a基因突變?cè)囼?yàn)評(píng)價(jià)新型染料溶劑紅207的堿基突變風(fēng)險(xiǎn)。方法 不同質(zhì)量濃度的溶劑紅207（0.625~10.000 μg/mL）分別與TA98和TA100混合于96孔培養(yǎng)板，在37℃條件下作用72 h后判斷其對(duì)突變菌落數(shù)的影響。在優(yōu)化后的體外L5178Y細(xì)胞Pig-a基因突變實(shí)驗(yàn)中，溶劑紅207（2.5~20.0 μg/mL）分別與L5178Y細(xì)胞在有或無S9代謝活化條件下作用24 h或4 h，于給藥后第8天評(píng)價(jià)其是否可誘導(dǎo)哺乳動(dòng)物細(xì)胞Pig-a基因的突變頻率增加。結(jié)果 無和有S9代謝活化條件下，溶劑紅207可導(dǎo)致TA98和TA100回復(fù)性突變孔數(shù)顯著增加（P<0.05、0.01、0.001），且存在濃度效應(yīng)相關(guān)性，代謝活化后增加更為明顯。在非S9代謝活化條件下，溶劑紅207各濃度組Pig-a基因突變率與陰性對(duì)照組比較無顯著性差異；在S9代謝活化條件下，溶劑紅207質(zhì)量濃度范圍為2.5~20 μg/mL時(shí)，可導(dǎo)致Pig-a基因突變率顯著增加（P<0.01、0.001），且存在濃度效應(yīng)關(guān)系。結(jié)論 首次使用體外高通量試驗(yàn)方法評(píng)價(jià)溶劑紅207的致突變風(fēng)險(xiǎn)，發(fā)現(xiàn)其存在體外致突變性且經(jīng)I相代謝活化后致突變性進(jìn)一步增強(qiáng)。

Objective To evaluate the base-pair mutation risk of a novel medicinal dye solvent red 207 by fluctuation Ames test based on Salmonella typhimurium and the in vitro Pig-a gene mutation assay based on mouse lymphoma cells (L5178Y). Methods Different concentrations of solvent red 207 (0.625-10.000 μg/mL) were mixed with TA98 and TA100 in 96-well culture plates, and its effects to the number of revertants were determined after a 72 h incubation at 37 ℃. In addition, solvent red 207 (2.5-20.0 μg/mL) were treated with L5178Y cells under the conditions with or without metabolic activation for 24 h or 4 h, and its effects to the frequency of Pig-a gene mutation in mammalian cells were evaluated on the 8th day after treatement. Results Both in the absence and presence of S9 metabolic conditions, the solvent red 207 ranges between 0.625-10 μg/mL led to significant increase in the number of TA98 and TA100 revertants (P<0.05, 0.01 and 0.001), and there was a concentration-effect correlation, and the extent of increase in the number of revertants are more obvious after the metabolism. In absence of S9 activation, the Pig-a gene mutation rates in cells treated with different concentrations of solvent red 207 showed no difference comparing to the vehicle control group; In the presence of S9 activation, solvent red 207 ranges between 2.5-20 μg/mL induced increase of the frequency of Pig-a gene mutation, and there is a certain concentration-effect relationship (P<0.01 and 0.001). Conclusion This study for the first time used the in vitro high-throughput test methods to evaluate the mutagenic risk of solvent red 207, and suggested that the solvent red 207 is mutagenic, while the mutagenicity could be further enhanced after the phase I metabolism.

R992

國家“重大新藥創(chuàng)制”科技重大專項(xiàng)（2018ZX09201017）；國家自然科學(xué)基金資助項(xiàng)目（81503347）