Inhibitory effects of combined administration of antibiotics and anti-inflammatory drugs on lung tumor development initiated by N-nitrosobis(2-hydroxypropyl)amine in rats

The effects of antibiotics and anti-inflammatory drugs on the promotion sta ge of lung carcinogenesis initiated with N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats were investigated in two experiments with a similar protocol , In experiment 1, rats received tap water containing 2000 p,p,m, BHP for 1 2 weeks followed by basal diet or basal diet containing 0.02% erythromycin (EM), 0.04% ampicillin (ABPC), 1.5% sho-saiko-to, 0.02% EM plus 1.5% shosai ko-to or 0.04% ABPC plus 1.5% sho-saiko-to for 8 weeks after BHP administra tion. The development of adenocarcinomas (AC), squamous cell carcinomas (Sq C) and adenosquamous carcinomas (ASqC) was completely inhibited in rats giv en ABPC plus sho-saiko-to and the numbers of lung lesions including alveola r hyperplasias, adenomas and carcinomas were decreased in rats given EM plu s sho-saiko-to or ABPC plus sho-saiko-to, Neutrophil and macrophage infiltr ation into alveolar spaces of the lung were also markedly suppressed. In ex periment 2, rats received BHP in the same manner as in experiment 1 and bas al diet or basal diet containing 0.04% ABPC, 0.006% piroxicam, 0.04% ABPC p lus 0.006% piroxicam and 0.04% ABPC plus 0.75% ougon for 8 weeks. The incid ence and number of carcinomas, including ACs, SqCs and ASqCs were decreased in rats given ABPC plus piroxicam or ABPC plus ougon, Bacteria, mainly Esc herichia coli, were detected in broncho-alveolar lavage of rats receiving B HP, The results suggest that chronic inflammation might be involved in the progression of lung carcinogenesis by BHP in rats and its suppression may t herefore be useful as a chemopreventive strategy in lung cancer clinics.