Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli country 350, Taiwan.
Environ Mol Mutagen. 2010 May;51(4):315-21. doi: 10.1002/em.20550.
Epidemiological studies have demonstrated that cooking oil fumes (COF) are an environmental risk factor for the development of lung adenocarcinoma among nonsmoking females in Taiwan. Aside from polycyclic aromatic hydrocarbons, aldehydes, especially trans, trans-2,4-decadienal (tt-DDE) are found to be abundant in COF. Although there is indication that tt-DDE induces DNA damage, the precise role of tt-DDE in the induction of DNA damage in lung cells is still not clear. When we assessed DNA breaks with the Comet assay, we found that the DNA breaks induced by 1 muM tt-DDE in human bronchial epithelial cells (BEAS-2B) could be significantly reduced by antioxidants, suggesting that oxidative stress was involved. Indeed, when tt-DDE-treated cells were coincubated with endonuclease III/formamidopyrimidine-DNA glycosylase or with nuclear extract (NE), an enhancement of DNA breaks was observed at 1 hr after tt-DDE exposure. Furthermore, when NE was incubated with an antibody against 8-oxoguanine DNA glycosylase (anti-OGG1), a reduction in tt-DDE/NE-induced DNA breaks could be demonstrated. Since OGG1 is a specific repair enzyme for 8-oxo-deoxyguanosine (8-oxo-dG), these findings indicated that 8-oxo-dG was involved. On the other hand, when NE was incubated with antibodies against nucleotide excision repair enzymes, there was a significant reduction in tt-DDE/NE-induced DNA breaks at 4 hr after tt-DDE treatment. These observations indicate that, in addition to early oxidative DNA damage, nonoxidative DNA damage such as bulky adduct formation, was also induced by tt-DDE. Our study further affirms that tt-DDE is genotoxic to human lung cells and can increase carcinogenic risk.
流行病学研究表明，烹调油烟（COF）是台湾地区不吸烟女性患肺腺癌的环境危险因素之一。除了多环芳烃外，醛类，尤其是反式，反式-2,4-癸二烯醛（tt-DDE）在 COF 中含量丰富。尽管有迹象表明 tt-DDE 会导致 DNA 损伤，但 tt-DDE 在诱导肺细胞 DNA 损伤的确切作用仍不清楚。当我们用彗星试验评估 DNA 断裂时，我们发现 1 μM tt-DDE 诱导人支气管上皮细胞（BEAS-2B）中的 DNA 断裂可以被抗氧化剂显著减少，这表明氧化应激参与其中。事实上，当 tt-DDE 处理的细胞与内切酶 III/甲酸嘧啶-DNA 糖基化酶或核提取物（NE）共孵育时，在 tt-DDE 暴露 1 小时后观察到 DNA 断裂的增强。此外，当 NE 与针对 8-氧鸟嘌呤 DNA 糖基化酶（anti-OGG1）的抗体孵育时，可以证明 tt-DDE/NE 诱导的 DNA 断裂减少。由于 OGG1 是 8-氧脱氧鸟苷（8-oxo-dG）的特异性修复酶，这些发现表明 8-oxo-dG 参与其中。另一方面，当 NE 与核苷酸切除修复酶的抗体孵育时，在 tt-DDE 处理后 4 小时，tt-DDE/NE 诱导的 DNA 断裂明显减少。这些观察结果表明，除了早期氧化 DNA 损伤外，tt-DDE 还会诱导非氧化 DNA 损伤，如大体积加合物的形成。我们的研究进一步证实 tt-DDE 对人肺细胞具有遗传毒性，并可能增加致癌风险。
