Li Guang-Yong, Lee Hye-Young, Choi You-Jin, Lee Mi-Ock, Shin Ho-Sang, Kim Hyeon-Young, Lee Sung-Bae, Lee Byung-Hoon
17College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul, 151-742 Korea.
27Department of Environmental Education and Abuse Drug Research Center, Kongju National University, Kongju, 314-701 Korea.
Toxicol Res. 2008 Sep;24(3):201-206. doi: 10.5487/TR.2008.24.3.201. Epub 2008 Sep 1.
Exposure to formaldehyde (FA) is closely associated with adverse health effects such as irritation, inflammation, and squamous cell carcinomas of the nasal cavities. Owing to its rapid metabolism and elimination, exposure to FA does not always result in an increased concentration in blood or urine of animals and humans. Therefore, the development of biomarkers for FA exposure is necessary for risk assessment. In the present study, the effects of FA were investigated on the expression of genes involved in the MAPK pathway in vitro and results confirmed in rats exposed to FA by inhalation. Treatment of Hs 680.Tr human tracheal epithelial cells with FA induced gene expression for PDGFA, TNFSF11, SHC1, and HRAS. HRAS expression was also increased in tracheas of rats exposed to FA In addition, FA exposure induced the expression of RASSF4, a member of the Rasassociation domain family of Ras effectors, in rat tracheas. In conclusion, data showed FA-inducible expression of genes involved in the MAPK pathway occurred and increased expression of HRAS and RASSF4 was noted in rat tracheas subchronically exposed to FA by inhalation. These genes may serve as molecular targets of FA toxicity facilitating the understanding of the toxic mechanism.
接触甲醛（FA）与不良健康影响密切相关，如鼻腔刺激、炎症和鳞状细胞癌。由于其快速代谢和消除，接触FA并不总是导致动物和人类血液或尿液中浓度升高。因此，开发FA暴露生物标志物对于风险评估是必要的。在本研究中，在体外研究了FA对丝裂原活化蛋白激酶（MAPK）途径相关基因表达的影响，并在吸入FA的大鼠中得到证实。用FA处理Hs 680.Tr人气管上皮细胞可诱导血小板衍生生长因子A（PDGFA）、肿瘤坏死因子配体超家族成员11（TNFSF11）、含SH2结构域的接头蛋白1（SHC1）和Harvey鼠肉瘤病毒癌基因同源物（HRAS）的基因表达。在暴露于FA的大鼠气管中，HRAS表达也增加。此外，FA暴露诱导大鼠气管中Ras效应器Ras关联结构域家族成员RASSF4的表达。总之，数据表明，在吸入FA的大鼠气管中，发生了FA诱导的MAPK途径相关基因表达，并且HRAS和RASSF4的表达增加。这些基因可能作为FA毒性的分子靶点，有助于理解其毒性机制。
