Department of Clinical Pharmacy, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Department of Pharmacy, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Environ Sci Pollut Res Int. 2018 Apr;25(10):10135-10140. doi: 10.1007/s11356-018-1539-8. Epub 2018 Feb 27.
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 in S. typhimurium strain TA97, TA98, TA100, TA102, or TA1535, regardless of the presence/absence of S9 activation. However, ultraviolet (UV) light-irradiated MTMP exhibited mutagenicity in S. typhimurium strain 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.
在以前的研究中,我们在静脉注射溶液中检测到了光引发剂 1-羟基环己基苯基酮(1-HCHPK)、甲基 2-苯甲酰苯甲酸酯(MBB)和 2-甲基-4'-(甲硫基)-2-吗啉基丙酰苯酮(MTMP)。此外,我们还报告称 1-HCHPK、MBB 和 MTMP 对正常人外周血单核细胞具有细胞毒性。先前的一项体外研究报道称,自由基光引发剂将共价结合的嘌呤残基引入 DNA 中。然而,对于 1-HCHPK、MBB 和 MTMP 的体外致突变性知之甚少。在本体外研究中,我们使用 Ames 试验评估了 1-HCHPK、MBB 和 MTMP 的致突变性。我们发现未经处理的 1-HCHPK、MBB 和 MTMP 在没有 S9 激活的情况下,对鼠伤寒沙门氏菌 TA97、TA98、TA100、TA102 或 TA1535 菌株均无致突变性。然而,在没有 S9 激活的情况下,紫外线(UV)照射的 MTMP 对鼠伤寒沙门氏菌 TA97 菌株具有致突变性。总之,我们认为暴露于包括静脉注射溶液中的 UV 照射的 MTMP 可能导致移码突变。