EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

近年来，雾化给药在肺癌化学预防中的可行性得到了证实。这种暴露途径具有将高浓度药剂应用于靶组织的额外优点，同时理论上最小化伴随的全身毒性。 当然，肺上皮细胞暴露于致癌物的途径绝大多数是由于吸入颗粒、雾化液体或气体。最近，布地奈德的雾化给药已显示出显著抑制A系小鼠肺中B[a]P诱导的腺瘤形成（Wattenberg等，Cancer Res. 57：5489-5492，1997）。本研究的目的是探讨四种化学预防剂，包括二氟甲基鸟氨酸（DFMO）和丙酸倍氯米松在这个模型中对肺癌的抑制作用。 叙利亚黄金肺癌模型正在与MNU一起使用，MNU是一种已知会诱导鳞状细胞癌的致癌物质。化学预防剂通过气雾剂输送。在MNU给药开始后30周，测定仓鼠的肺部病变和癌形成。记录具有肺肿瘤的动物的数目、每只动物的肺肿瘤数目和每只携带肿瘤的动物的肺肿瘤数目。切除所有肿瘤并进行组织学检查，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.