EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

近年来，气溶胶给药策略在肺癌化学预防中的可行性得到了验证。这种暴露途径还有一个额外的优点，即对目标组织施加高浓度的药剂，同时理论上最小化全身毒性。当然，肺上皮接触致癌物的途径绝大多数是由于吸入微粒、雾化液体或气体。最近，布地奈德雾化给药已被证明能显著抑制B[a]P诱导的a株小鼠肺腺瘤的形成（Wattenberg et al., Cancer, 57:5489-5492, 1997）。本研究的目的是研究四种化学预防药物，包括二氟甲基鸟氨酸（DFMO）和二丙酸倍氯米松对该模型肺癌的抑制作用。叙利亚金肺癌模型正在与MNU一起使用，MNU是一种已知会诱发鳞状细胞癌的致癌物。化学预防剂通过气雾剂输送。在MNU开始给药30周后，对仓鼠进行肺部病变和癌形成检测。记录肺肿瘤动物数、每只动物肺肿瘤数、每只荷瘤动物肺肿瘤数。所有肿瘤均切除，进行组织学检查，并对每个肿瘤进行病理诊断。

The feasibility of aerosol drug delivery strategy for the chemoprevention of pulmonary cancer has been validated recently. This route of exposure has the added advantage of applying a high concentration of agent to the target tissue while theoretically minimizing attending systemic toxicity. Certainly the route of exposure of the pulmonary epithelia to carcinogens is overwhelmingly due to inhalation of particulates, aerosolized liquids, or gases. Recently the aerosolized administration of budesonide has been shown to markedly inhibit B[a]P induced adenoma formation in lungs of the Strain A mouse (Wattenberg et al., Cancer Res. 57:5489-5492, 1997). The objective of this study is to investigate the efficacy of four chemopreventive agents including Difluoromethylornithine (DFMO) and Beclomethasone dipropionate to inhibit lung cancer in this model. The Syrian Golden lung cancer model is being used with MNU, a carcinogen known to induce squamous cell carcinomas. Chemopreventive agents are being delivered by aerosol. At 30 weeks after the beginning of MNU administrations the hamsters are being assayed for pulmonary lesions and carcinoma formation. The number of animals with lung tumors, the number of lung tumors per animal, and the number of lung tumors per tumor-bearing animal is recorded. All tumors are excised and examined histologically and a pathological diagnosis made on each tumor.