EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

气雾剂给药策略用于肺癌的化学预防的可行性最近已得到验证。这种暴露途径还有一个额外的好处，就是在理论上将全身毒性降至最低的同时，对目标组织应用了高浓度的制剂。当然，肺上皮细胞接触致癌物的途径绝大多数是由于吸入颗粒物、雾化液体或气体。最近，雾化给药布地奈德已被证明显著抑制B[a]P诱导的A品系小鼠肺部腺瘤的形成(Wtenberg等人，癌症研究57：5489-5492,1997)。本研究的目的是观察二氟甲基鸟氨酸(DFMO)和二丙酸倍氯米松四种化学预防药物对肺癌的抑制作用。叙利亚金色肺癌模型正在与MNU一起使用，MNU是一种已知可诱发鳞状细胞癌的致癌物质。化学预防药物正通过气雾剂运送。在开始注射MNU 30周后，正在对仓鼠进行肺部病变和癌症形成的检测。记录有肺肿瘤的动物数量、每只动物的肺肿瘤数量和每只荷瘤动物的肺肿瘤数量。所有肿瘤都被切除，并进行组织学检查，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.