2005-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/694405摘要：嚼食檳榔和罹患口腔鱗狀上皮細胞癌以及口腔黏膜下纖維化等疾病密切相關。實驗證據顯示鱗狀上皮細胞癌的病變原因和病人免疫機能的惡化有密切關聯性，口腔癌和口腔黏膜下纖維化病人，與正常的對照組比較，其T細胞和B細胞免疫反應明顯變差，且在病變組織中有較多的免疫細胞浸潤，進一步分析發現在口腔病變組織中的免疫細胞主要是T細胞，其中大部分細胞處於活化狀態且CD4+細胞/CD8+細胞的比值明顯升高。口腔鱗狀上皮細胞癌病人T細胞的增生以及表現細胞激素IL-2和IFN-的能力下降，而在口腔癌前病變的病人，也同樣發現類似的細胞免疫功能和細胞激素表現下降的現象，上述結果顯示T細胞免疫反應的改變在口腔癌和口腔黏膜下纖維化的病變過程中可能扮演著重要的角色。然而，截至目前為止，文獻缺乏有關檳榔成份對T細胞的免疫毒理學研究，計畫申請人先前受國科會支持的研究計畫成果指出，檳榔萃取物對T細胞的增生、存活率以及細胞激素基因表現具有直接的抑制作用；進一步的試驗結果發現檳榔萃取物會誘發T細胞染色體呈現DNA laddering的現象，顯示檳榔萃取物抑制細胞激素的作用機制可能和其造成細胞凋亡的細胞毒性有關。因此，本計劃的主要目的在<br> Abstract: Betel quid chewing is associated with an increased risk of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). Experimental evidence suggests that the pathogenesis of squamous cell carcinoma is associated with deterioration in the immunological status. Deficiencies in both T and B cell-mediated immune responses have been reported in patients with oral cancers or OSF. Histological studies showed an increased infiltration of immune cells in oral tissue specimens from patients with oral carcinoma or OSF. The major immunocompetent cells found in the oral lesions were T lymphocytes with an increased CD4+ to CD8+ ratio. Diminished proliferative capability and IFN- and IL-2 expression in T lymphocyte were found in immune cells isolated from patients with OSCC or oral precancerous lesions. Together these findings indicate that depressed T cell reactivity may play a role in the pathophysiology of oral cancer and OSF. However, little is known with respect to the direct influence of betel quid components on T-cell reactivity. Results of the applicant’s previous studies demonstrated that areca nut extracts (ANE), but not the areca alkaloids arecoline and arecaidine, produced a direct inhibitory effect on T-cell proliferation, viability and cytokine secretion. Preliminary results further showed an induction of DNA laddering in murine EL4 T cells by ANE treatment, suggesting that the ANE-induced inhibition of cytokine expression may be due to its cytotoxic effects on T cells. In light of the above findings, the objective of the proposed research project is to critically investigate the cytotoxic effect of ANE on T cells and to study its possible underlying mechanism. The results from this project will provide further insights into our understanding to the potential immunotoxicity of areca nut, the major component of betel quid, on T cells.檳榔免疫毒性細胞凋亡細胞激素細胞毒性areca nutT cellapoptosiscytokinecytotoxicity