N-Nitrosobis (2-hydroxypropyl) amineによる実験的ラット肺発癌に対する抗菌薬 : clarithromycinとcyclooxygenase-2 inhibitor : etodolacによる抑制効果

Abstract

The inhibitory effects of antibiotics and a cyclooxygenase(COX)-2 in- hibitor on lung carcinogenesis in rats initiated with N-nitrosobis(2-hydroxypropyl)amine (BHP) were investigated. Male Wistar rats were given tap water without BHP or tap water containing 2000 ppm BHP with a basal diet for 12 weeks followed by the basal diet or the diet containing test compounds for 8 weeks. Rats received basal diet or diets containing 0.02% clarithromycin (CAM), 0.015% etodolac, 0.02% CAM plus 0.015% etodolac, respectively. The incidences of lung lesions were not different but the numbers of lesions including adenocarcinoma (AC), squamous cell carcinoma (SCC) and adenos- quamous carcinoma (ASCC) decreased in rats given CAM, etodolac or CAM plus etodolac as compared with those in rats given no drugs. In the lungs of rats which received the drugs, the suppression of chronic inflammation in the alveolar spaces and walls was evident. The labeling index of proliferating cell nuclear antigen (PCNA) decreased in alveplar hyper- plasia (AH) in the lungs of rats which received CAM, etodolac and CAM plus etodolac ; however, 8-hydroxydeoxyguanosine (8-OHdG) generation studied by immunohistochemis- try did not differ between the lungs of rats with or without the administration of drugs. The results indicate that the suppression of chronic inflammation may inhibit the progression of lung carcinogenesis by BHP in rats and possibly provide a chemotherapeutic strategy for controlling advanced lung cancer.