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Carcinogenesis, Vol. 21, No. 2, 251-256, February 2000
© 2000 Oxford University Press

Carcinogenesis

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

Masahiro Tsutsumi1, Hiromichi Kitada, Kazumi Shiraiwa, Makoto Takahama, Toshifumi Tsujiuchi, Hiroyuki Sakitani, Yasutaka Sasaki, Koichi Murakawa, Masatoshi Yoshimoto and Yoichi Konishi

Department of Oncological Pathology, Cancer Center, Nara Medical University, 840 Shijo-cho Kashihara, Nara, 634 Japan

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.

Abbreviations: AC, adenocarcinoma; ABPC, ampicillin; Ad, adenoma; AH, alveolar hyperplasia; ASqC, adenosquamous carcinoma; BAL, broncho-alveolar lavage; BHP, N-nitrosobis (2-hydroxypropyl)amine; EM, erythromycin; NSAID, non-steroidal anti-inflammatory drug; PCNA, proliferating cell nuclear antigen; SM, squamous metaplasia; SqC, squamous cell carcinoma.


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