UV-irradiated 2-methyl-4′-(methylthio)-2-morpholinopropiophenone-containing injection solution produced frameshift mutations in the Ames mutagenicity assay
UV-irradiated 2-methyl-4′-(methylthio)-2-morpholinopropiophenone-containing injection solution produced frameshift mutations in the Ames mutagenicity assay
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DOI：
10.1007/s11356-018-1539-8
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发表时间：
2018-02
影响因子：
5.8
通讯作者：
Mariko Takai;Yoichi Kawasaki;S. Arimoto;Yusuke Tanimoto;Y. Kitamura;T. Sendo
中科院分区：
文献类型：
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作者：
Mariko Takai;Yoichi Kawasaki;S. Arimoto;Yusuke Tanimoto;Y. Kitamura;T. Sendo
在以前的研究中，我们检测到静脉注射液中的光引发剂1-羟基环己基苯基酮（1-HCHPK），2-苯甲酰基苯甲酸甲酯（MBB）和2-甲基-4 ′-（甲硫基）-2-吗啉基苯丙酮（MTMP）。此外，我们报道，1-HCHPK，MBB，和MTMP表现出对正常人外周血单个核细胞的细胞毒性。先前的体外研究报道，自由基光引发剂将共价结合的嘌呤残基引入DNA中。然而，很少有人知道1-HCHPK，MBB，MTMP的体外致突变性。在本体外研究中，我们使用艾姆斯试验评价了1-HCHPK、MBB和MTMP的致突变性。我们发现未处理的1-HCHPK、MBB和MTMP在鼠伤寒沙门氏菌菌株TA 97、TA 98、TA 100、TA 102或TA 1535中无致突变性，无论是否存在S9活化。然而，紫外线（UV）照射的MTMP在没有S9活化的情况下对鼠伤寒沙门氏菌菌株TA 97表现出致突变性。总之，我们认为暴露于紫外线照射的MTMP，包括静脉注射液，可导致移码突变。
In previous studies, we detected the photoinitiators 1-hydroxycyclohexyl phenyl ketone (1-HCHPK), methyl 2-benzoylbenzoate (MBB), and 2-methyl-4′-(methylthio)-2-morpholinopropiophenone (MTMP) in intravenous injection solutions. In addition, we reported that 1-HCHPK, MBB, and MTMP exhibited cytotoxicity towards normal human peripheral blood mononuclear cells. A previous in vitro study reported that a free-radical photoinitiator introduced covalently bound purine residues into DNA. However, little is known about the in vitro mutagenicity of 1-HCHPK, MBB, and MTMP. In the present in vitro study, we evaluated the mutagenicity of 1-HCHPK, MBB, and MTMP using the Ames test. We found that untreated 1-HCHPK, MBB, and MTMP were not mutagenic inS. typhimuriumstrain TA97, TA98, TA100, TA102, or TA1535, regardless of the presence/absence of S9 activation. However, ultraviolet (UV) light-irradiated MTMP exhibited mutagenicity inS. typhimuriumstrain TA97 in the absence of S9 activation. In conclusion, we suggest that exposure to UV-irradiated MTMP, including in intravenous injection solutions, can result in frameshift mutations.