N-NITROSOBIS (2-HYDROXYPROPYL) AMINEによる実験的ラット肺発癌に対する抗生物質, 非ステロイド系抗炎症薬および生薬の併用投与による効果

Abstract

The efficacy of combined adrninistration of antibiotics, nonsteroidal anti- inflammatory drug (NSAID) and herbal medicines on lung carcinogenesis were investigat- ed in rats treated with N-nitrosobis (2-hydroxypropyl) amine (BHP). This study consisted of two experiments. In both experiments, 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. In experiment 1, rats received basal diet alone or diets containing 0.02% erythromycin (EM), 0.04% ampicillin (ABPC), 1.5% sho' -saiko-to, 0.02% EM plus 1.5% sho-saiko-to or 0.04% ABPC plus 1.5% sho-saiko-to, respectively. The incidences of adenocarcinoma (AC) and non-small cell carcinomas including AC were completely inhibited in rats given ABPC plus sho-saiko-to, and the numbers of alveolar hyperplasia (AH) and total lung lesions including AH, adenoma (Ad) and AC, squamous metaplasia, squamous cell carcinoma (SqC) and adenosquamous car- cinoma (ASqC) were decreased in rats given ABPC plus sho-saiko-to or EM plus sho-saiko -to. In experiment 2, rats received basal diet alone or diets containing 0.04% ABPC, 0.006% piroxicam, 0.04% ABPC plus 0.006% piroxicam or 0.04% ABPC plus 0.75% ogon, respectively. The incidences and numbers of AC and non-small cell carcinomas including AC were decreased in rats given ABPC plus piroxicam or ABPC plus ogon. The inflamma- tory reactions in lung lesions were reduced in rats given ABPC plus sho-saiko-to or ABPC plus piroxicam in experiment 1 or 2. These results suggest that combined administration of antibiotics and NSAID or herbal medicines inhibits the progression of lung car- cinogenesis in rats initiated with BHP as a result of suppression of chronic inflammation. Therefore, the continuous inflammatory reaction may exert itself as a promoting factor.