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 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.
Tsutsumi
M
M
Department of Oncological Pathology, Cancer Center, Nara Medical University, 840 Shijo-cho Kashihara, Nara, 634 Japan.
Kitada
H
H
Shiraiwa
K
K
Takahama
M
M
Tsujiuchi
T
T
Sakitani
H
H
Sasaki
Y
Y
Murakawa
K
K
Yoshimoto
M
M
Konishi
Y
Y
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control*; D000667:Ampicillin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D002273:Carcinogens / Q000633:toxicity*; D018196:Carcinoma, Adenosquamous / Q000139:chemically induced / Q000517:prevention & control*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000517:prevention & control*; D003043:Cocarcinogenesis; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D004917:Erythromycin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009602:Nitrosamines / Q000633:toxicity*; D010406:Penicillins / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D010894:Piroxicam / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts; D018410:Pneumonia, Bacterial / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D031364:Scutellaria baicalensis; D013047:Specific Pathogen-Free Organisms
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D004365:Drugs, Chinese Herbal; D009602:Nitrosamines; D010406:Penicillins; D010936:Plant Extracts; C499814:Scutellaria baicalensis extract; D010894:Piroxicam; C012457:diisopropanolnitrosamine; C018142:saiko-keishi-to; D004917:Erythromycin; D000667:Ampicillin