Schwartz J L, Shklar G, Flynn E, Trickler D
Harvard School of Dental Medicine, Department of Oral Pathology and Oral Medicine, Boston, MA 02115.
Adv Exp Med Biol. 1990;262:77-93. doi: 10.1007/978-1-4613-0553-8_7.
In the past four years this laboratory has utilized the hamster cheek pouch tumor model to investigate the anticancer activities of antioxidants, such as beta carotene. These molecules, which have exhibited no evidence of toxicity, have been administered systemically (oral ingestion), and locally to the tumor site in the hamster cheek pouch. The results have been either the inhibition of tumor growth, or the regression of tumor. Adjacent to the degenerating tumors a dense inflammatory infiltrate was observed. Specifically, the cytokines, tumor necrosis factor alpha, and beta, have been immunohistochemically localized to the site of regressed oral carcinoma. Recently, liposomes composed of phosphaditylcholine, phosphaditylserine, and phosphodityelanolamine were combined with beta carotene and injected locally to oral squamous cell carcinoma of the hamster. The results indicated that tumor cells accumulated the liposomes and were lysed while normal mucosal cells did not demonstrate this effect. Therefore antioxidants such as beta carotene can be localized to a tumor site, without a toxic response. Future studies on the anticancer activity of the antioxidants need to focus on the cellular and molecular changes produced in the immune effectors and in the mucosal cells following administration of the antioxidants.
在过去四年中，本实验室利用仓鼠颊囊肿瘤模型来研究抗氧化剂（如β-胡萝卜素）的抗癌活性。这些未显示出毒性迹象的分子，已通过全身给药（口服摄入）以及局部给药至仓鼠颊囊的肿瘤部位。结果要么是肿瘤生长受到抑制，要么是肿瘤消退。在退化的肿瘤附近观察到密集的炎性浸润。具体而言，细胞因子肿瘤坏死因子α和β已通过免疫组织化学定位到消退的口腔癌部位。最近，由磷脂酰胆碱、磷脂酰丝氨酸和磷脂酰乙醇胺组成的脂质体与β-胡萝卜素结合，并局部注射到仓鼠的口腔鳞状细胞癌中。结果表明，肿瘤细胞积累了脂质体并被裂解，而正常黏膜细胞未表现出这种效应。因此，诸如β-胡萝卜素之类的抗氧化剂可以定位于肿瘤部位，而无毒性反应。未来对抗氧化剂抗癌活性的研究需要关注抗氧化剂给药后免疫效应器和黏膜细胞中产生的细胞和分子变化。
