Pulmonary carcinogenesis in mice with a single intratracheal instillation of 9, 10-dimethyl benz[a]anthracene

A single intratracheal instillation of 9,10-dimethyl benz(a)anthracene (DMBA) at 3 different doses of 5, 10, and 20 mg/kg body weight to Balb/c mice for 12 weeks had caused a significant incidence of pulmonary tumors along with inflammatory changes. The number of macrophages in the broncho-alveolar lavage (BAL) fluid increased significantly, while the neutrophil and lymphocyte count as well as the protein content in the BAL fluid remained unchanged. A marked elevation in the lipid peroxidation product as well as the antioxidative enzymes were noted in the DMBA-treated group. The BAL fluid, which contains the surfactant membrane, was tested for rotational diffusion of the small hydrocarbon fluorophore, diphenyl hexatriene, and resulted in an enhanced fluorescence polarization and anisotropy value as well as the order parameter. DMBA treatment also altered the toxicity parameters, such as the lipid peroxidation, catalase, total protein, reduced glutathione, and alanine and amino transferase activities in the liver and kidney tissues. The results suggest that DMBA-induced lung tumor development in Balb/c mice could be an important model for the study of pathophysiology of BAL-fluid-associated surfactant and offers to test a variety of promising chemopreventive/chemotherapeutic agents.