EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS IN ANIMAL MOD

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。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）（气雾剂）、zileuton（饮食和气雾剂）、舒林酸，以及DFMO和布地奈德、舒林酸和布地奈德联合使用对该模型肺癌的抑制效果。A系小鼠肺癌模型正在与苯并[A]芘一起使用，苯并[A]芘是一种已知会诱发肺腺瘤的致癌物。化学预防剂主要通过气雾剂输送。B[a]P给药16周后，检测小鼠肺病变和腺瘤形成情况。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. The objective of this study is to investigate the efficacy of four chemopreventive agents including: difluoromethylornithine (DFMO) (aerosol), zileuton (diet and aerosol), sulindac, and combinations of DFMO and budesonide, and sulindac and budesonide to inhibit lung cancer in this model. The Strain A Mouse lung cancer model is being used with benzo[a]pyrene, a carcinogen known to induce lung adenomas. Chemopreventive agents are being primarily delivered by aerosol. At 16 weeks after the beginning of B[a]P administrations the mice are being assayed for pulmonary lesions and adenoma 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.