| Summary: | 博士 === 國立成功大學 === 環境醫學研究所 === 98 === In Taiwan, the number of construction workers is about 8 hundred thousand, which represents 12% of the total working population. In previous studies, the prevalence of occupational skin diseases among construction workers was as high as 21%. It was the leading cause of occupational diseases in Taiwan. The majority of construction workers are cement workers and irritant cement contact dermatitis and allergic cement contact dermatitis rate as two of the most prevalent occupational dermatoses. The major cause of allergic cement contact dermatitis is hexavalent chromium. The prevalence of chromium hypersensitivity in Taiwanese cement workers was shown to be around 13%, which is more than twenty- fold when compared to the general population. The prognosis of chromium hypersensitivity is poor and workers who are continually exposed to cement are susceptible to its repeated recurrence. The detailed pathogenesis of chromium hypersensitivity remains unknown. The aims of our study are to investigate the pathogenic molecular mechanisms of chromium hypersensitivity, attempt to find potential chemopreventative agents to prevent the development of chromium hypersensitivity, as well as to discover the genetic background for cement workers with a chromium hypersensitivity disposition.
We found that hexavalent chromium could increase ROS formation, activate the Akt, NF-kB, and MAPK pathways, as well as increase the production of cytokines, including TNF-α and IL-1α in keratinocytes. The release of these cytokines from keratinocytes is considered to be a key participant in the pathogenesis of contact hypersensitivity.
In addition, we clearly demonstrated, in a coadjuvant chromium-sensitized albino guinea pig model, that the use of NAC could effectively reduce H2O2 and MDA levels in skin, increase the ORAC in plasma, and significantly decrease the sensitization rate of chromium hypersensitivity, Therefore, NAC could be a potential agent to prevent the development of chromium hypersensitivity in those workers who are unavoidably exposed to work-related chromium.
With regards to the genetic background of cement workers prone to chromium hypersensitivity, we found a genetic predisposition of TNF-α-308 GA genotype and GST-T1 null genotype to chromium sensitization.
Future studies will focus on the detailed molecular mechanisms of hexavalent chromium on keratinocytes by utilizing different types of antioxidants and specific Akt, NF-kB, MAPK inhibitors and anti-cytokines, to elucidate the relationships between ROS, cell signaling pathways and cytokine production in keratinocytes after exposure to hexavalent chromium. We would also like to utilize these new findings, plus well-established animal models and laboratory techniques to find out the detailed mechanisms of contact hypersensitivity with regards other common environmental or occupational related allergens, such as nickel, cobalt and fragrances, as well as probe new possible therapeutic and chemopreventative agents to help those who are subjected to regular contact with these allergens.
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