Kasai Hiroshi, Kawai Kazuaki
Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu 8078555, Japan.
ACS Omega. 2021 Apr 28;6(18):12014-12021. doi: 10.1021/acsomega.1c00614. eCollection 2021 May 11.
Epidemiological studies have revealed that alcohol, red meat, and cooking oil (or linoleate) are risk factors for both gastric and colon cancers. A survey of the mutation spectra of the p53 tumor suppressor gene in these cancers suggested that the types of mutations and the hot spots are similar to those induced by acetaldehyde (AcAld) in an in vitro p53 mutation analysis system. Accordingly, various combinations of possible factors, components, or model compounds were reacted in an emulsion and tested for the generation of AcAld. Efficient AcAld formation was only observed with combinations of three factors, red meat homogenate (or heme/myoglobin), methyl linoleate, and ethanol, but not by any combination of the two. The generated AcAld levels (ca. 500 μM) far exceeded the minimum mutagenic concentration (40-100 μM) obtained using concentrations of meat homogenate (or heme/Mb), linoleate, and ethanol comparable to those in the stomach after an ordinary meal. A mutagenic level of AcAld (75 μM) was also generated with a physiological concentration of ethanol, heme, and linoleate in the colon. As a mechanism, linoleate hydroperoxide formation and its decomposition in the presence of myoglobin (or heme) to generate the OH radical seem to be involved in the ethanol-to-AcAld conversion.
流行病学研究表明，酒精、红肉和食用油（或亚油酸酯）是胃癌和结肠癌的风险因素。对这些癌症中p53肿瘤抑制基因突变谱的一项调查显示，这些癌症中的突变类型和热点与体外p53突变分析系统中乙醛（AcAld）诱导的突变相似。因此，将各种可能的因素、成分或模型化合物组合在乳液中反应，并测试AcAld的生成情况。仅在红肉匀浆（或血红素/肌红蛋白）、亚油酸甲酯和乙醇这三种因素组合时观察到高效的AcAld形成，而任意两种因素的组合都不会形成。生成的AcAld水平（约500μM）远远超过了使用与普通餐后胃中肉匀浆（或血红素/肌红蛋白）、亚油酸酯和乙醇浓度相当的浓度所获得的最低诱变浓度（40 - 100μM）。在结肠中，生理浓度的乙醇、血红素和亚油酸酯也会生成诱变水平的AcAld（75μM）。作为一种机制，亚油酸酯氢过氧化物的形成及其在肌红蛋白（或血红素）存在下分解产生羟基自由基似乎参与了乙醇向AcAld的转化。
