Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka, 560-8531, Japan.
Research Center for Environmental Quality Management, Kyoto University, 1-2 Yumihama, Ohtsu, Shiga, 520-0811, Japan.
Sci Rep. 2019 Jan 24;9(1):660. doi: 10.1038/s41598-018-37239-6.
Carcinogens often generate mutable DNA lesions that contribute to cancer and aging. However, the chemical structure of tumorigenic DNA lesions formed by acetaldehyde remains unknown, although it has long been considered an environmental mutagen in alcohol, tobacco, and food. Here, we identify an aldehyde-induced DNA lesion, forming an intrastrand crosslink between adjacent guanine bases, but not in single guanine bases or in other combinations of nucleotides. The GG intrastrand crosslink exists in equilibrium in the presence of aldehyde, and therefore it has not been detected or analyzed in the previous investigations. The newly identified GG intrastrand crosslinks might explain the toxicity and mutagenicity of acetaldehyde in DNA metabolism.
致癌物通常会产生可突变的 DNA 损伤，从而导致癌症和衰老。然而，尽管乙醛长期以来一直被认为是酒精、烟草和食物中的环境诱变剂，但由其形成的致癌性 DNA 损伤的化学结构仍然未知。在这里，我们鉴定出一种醛诱导的 DNA 损伤，它在相邻的鸟嘌呤碱基之间形成链内交联，但不在单个鸟嘌呤碱基或其他核苷酸组合中形成。在醛存在的情况下，GG 链内交联处于平衡状态，因此在以前的研究中未被检测或分析。新鉴定的 GG 链内交联可能解释了乙醛在 DNA 代谢中的毒性和致突变性。
