Tsutsumi M, Kitada H, Shiraiwa K, Takahama M, Tsujiuchi T, Sakitani H, Sasaki Y, Murakawa K, Yoshimoto M, Konishi Y
Department of Oncological Pathology, Cancer Center, Nara Medical University, 840 Shijo-cho Kashihara, Nara, 634 Japan.
Carcinogenesis. 2000 Feb;21(2):251-6. doi: 10.1093/carcin/21.2.251.
The effects of antibiotics and anti-inflammatory drugs on the promotion stage 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 12 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% sho-saiko-to or 0.04% ABPC plus 1.5% sho-saiko-to for 8 weeks after BHP administration. The development of adenocarcinomas (AC), squamous cell carcinomas (SqC) and adenosquamous carcinomas (ASqC) was completely inhibited in rats given ABPC plus sho-saiko-to and the numbers of lung lesions including alveolar hyperplasias, adenomas and carcinomas were decreased in rats given EM plus sho-saiko-to or ABPC plus sho-saiko-to. Neutrophil and macrophage infiltration into alveolar spaces of the lung were also markedly suppressed. In experiment 2, rats received BHP in the same manner as in experiment 1 and basal diet or basal diet containing 0.04% ABPC, 0.006% piroxicam, 0.04% ABPC plus 0.006% piroxicam and 0.04% ABPC plus 0.75% ougon for 8 weeks. The incidence and number of carcinomas, including ACs, SqCs and ASqCs were decreased in rats given ABPC plus piroxicam or ABPC plus ougon. Bacteria, mainly Escherichia coli, were detected in broncho-alveolar lavage of rats receiving BHP. The results suggest that chronic inflammation might be involved in the progression of lung carcinogenesis by BHP in rats and its suppression may therefore be useful as a chemopreventive strategy in lung cancer clinics.
在两项采用相似方案的实验中，研究了抗生素和抗炎药对用N-亚硝基双（2-羟丙基）胺（BHP）引发大鼠肺癌促癌阶段的影响。在实验1中，大鼠饮用含2000 ppm BHP的自来水12周，之后给予基础饲料或含0.02%红霉素（EM）、0.04%氨苄青霉素（ABPC）、1.5%小柴胡汤、0.02% EM加1.5%小柴胡汤或0.04% ABPC加1.5%小柴胡汤的基础饲料，持续8周。给予ABPC加小柴胡汤的大鼠中腺癌（AC）、鳞状细胞癌（SqC）和腺鳞癌（ASqC）的发生完全受到抑制，给予EM加小柴胡汤或ABPC加小柴胡汤的大鼠中包括肺泡增生、腺瘤和癌在内的肺部病变数量减少。肺肺泡空间中的中性粒细胞和巨噬细胞浸润也明显受到抑制。在实验2中，大鼠以与实验1相同的方式接受BHP，并给予基础饲料或含0.04% ABPC、0.006%吡罗昔康、0.04% ABPC加0.006%吡罗昔康以及0.04% ABPC加0.75%欧甘的基础饲料，持续8周。给予ABPC加吡罗昔康或ABPC加欧甘的大鼠中包括AC、SqC和ASqC在内的癌的发生率和数量减少。在接受BHP的大鼠支气管肺泡灌洗中检测到主要为大肠杆菌的细菌。结果表明，慢性炎症可能参与了BHP诱导的大鼠肺癌进展，因此抑制慢性炎症可能作为肺癌临床中的化学预防策略。
