檳榔是部分國人經常使用的一種嚼塊，也是在引起口腔癌方面最廣被多數人探討的一環。在過往的許多論文中，檳榔嚼塊的各種水溶性及非水溶性的成分已被探討，包括基因毒性、致突變性以及口服後對動物的毒性，但是在口腔癌症生成的角色及過程除了流病調查有絕對的關係性外，其直接證據較薄弱。根據我們初步的觀察，我們認為檳榔嚼塊也許是在癌生成的過程中扮演了癌促進劑（Tumor promoter）的作用，因此本研究利用促癌作用模式以Benzo(a)pyrene當作癌起始劑，另外購買二種市售檳榔嚼塊（紅灰及未處理的檳榔子），抽取其水層萃取物當作癌促進劑塗抹於CD-1品系雌性小白鼠皮上觀察其癌症發生的過程，並且利用癌促進作用指標來證明檳榔及其添加物促進癌症生成的作用。本研究證實檳榔有腫瘤促進作用，經檳榔水萃取物塗抹CD-1小白鼠背部，可增加表皮厚度及Leukocyte infiltration，產生H/sub 2/O/sub 2/及上皮Myeloperoxidase活性，增加Ornithine decarboxylase活性，在檳榔添加Lime-piper添加料之水萃取物中有加強之作用，由於腫瘤促進之分子機制已被提出，包括過氧化作用，PKC活化等，本研究也發現檳榔及添加物Lime-piper有促進上皮組織PKC活化作用及促進NF-κB蛋白表現等，此作用在含lime-piper之檳榔更顯著。在流病調查上顯示口腔癌與檳榔之密切關係，但在基礎除了間接在基因毒性，突變性上之研究外，缺少了直接之證據說明檳榔在口腔癌作用形成之角色，本研究顯示檳榔有“腫瘤促進作用”之作用，其Lime-piper有加強此作用之能力。 Components of betel quid investigated for genotoxicity, mutagenicity, and animal toxicity. However, little information exists regarding the potential carcinogenicity to form oral betel quid. Considerable attention is focused in tumor promoters that occur environmentally for human uptake. In this study, the tumor promoting effect betel quid in benzo (a) pyrene intiated CD-1 mouse skin was investigated. In the present study, we found that betel quid (NB) and lime piper betel (LPB) at concentrations of 25, 50, and 75mg/ml, respectively, not only caused significant induction of hyperplasia, but also epidermal ornithine decarboxylase (ODC). Treatment of mouse skin with LPB caused production of H/sub 2/O/sub 2/ by 2.41-, 3.90-, and 3.76- fold, respectively, and marked induction of myeloperexidase (MPO) by 1.43-, 2.70-, and 2.29- fold. Application of the same amount of LPB also caused significant induction of PKC expression. These results indicated that NB and LPB have the potential as a promoting agent and the LP (lime-piper) play a major role in promoting effect of skin hyperplasia and inflammation. The tumor promoting effect of NB and LPB in mouse skin was associated with the induction of PKC and NF-κB.
