甲基丙烯酸缩水甘油酯致肺癌的分子机制及NQO1的潜在作用：研究进展与展望

Glycidyl Methacrylate-Induced Lung Carcinogenesis and the Potential Role of NQO1: Progress and Perspectives

摘要: 甲基丙烯酸缩水甘油酯(GMA)是一种具有明确遗传毒性的工业化学品，长期吸入暴露可诱导鼻腔及肺部肿瘤发生。体外研究表明，GMA可通过激活多条信号通路、诱导表观遗传改变以及调控长链非编码RNA表达等机制，促进人支气管上皮细胞恶性转化，上述分子事件均与细胞氧化还原失衡密切相关。NQO1作为Nrf2下游关键的II相解毒酶，通过清除醌类化合物及活性氧，在维持细胞氧化还原稳态中发挥核心作用。大量证据表明，NQO1在肺癌等多种肿瘤中异常表达，并通过调控代谢重编程、稳定突变型抑癌蛋白及激活促癌信号通路等机制促进肿瘤进展。然而，目前尚无研究直接探讨NQO1是否参与GMA诱导的肺癌发生过程。基于GMA诱导氧化应激与NQO1抗氧化/解毒功能之间的理论联系，NQO1极有可能在GMA致肺癌过程中发挥重要作用，但尚需实验验证。未来应深入开展细胞与分子生物学研究及人群流行病学调查，以阐明NQO1在GMA致肺癌中的确切角色，为职业暴露人群的风险评估和干预策略开发提供科学依据。

Abstract: Glycidyl methacrylate (GMA) is an industrial chemical with confirmed genotoxicity. Long-term inhalation exposure can induce tumors in the nasal cavity and lungs. In vitro studies have shown that GMA promotes malignant transformation of human bronchial epithelial cells through mechanisms involving the activation of multiple signaling pathways, induction of epigenetic alterations, and regulation of long non-coding RNA expression. These molecular events are closely associated with cellular redox imbalance. NQO1, a key phase II detoxifying enzyme downstream of Nrf2, plays a central role in maintaining cellular redox homeostasis by eliminating quinoid compounds and reactive oxygen species. Accumulating evidence indicates that NQO1 is aberrantly expressed in various tumors, including lung cancer, and promotes tumor progression through mechanisms such as regulating metabolic reprogramming, stabilizing mutant tumor suppressor proteins, and activating oncogenic signaling pathways. However, no study to date has directly investigated whether NQO1 is involved in GMA-induced lung carcinogenesis. Based on the theoretical link between GMA-induced oxidative stress and the antioxidant/detoxifying functions of NQO1, it is highly plausible that NQO1 plays an important role in GMA-induced lung cancer, though experimental validation is urgently needed. Future studies should focus on in-depth cellular and molecular biological investigations as well as population-based epidemiological surveys to elucidate the precise role of NQO1 in GMA-induced lung carcinogenesis, thereby providing scientific evidence for risk assessment and intervention strategies in occupationally exposed populations.