The lung tumor promoter, butylated hydroxytoluene (BHT), causes chronic inflammation in promotion-sensitive BALB/cByJ mice but not in promotion-resistant CXB4 mice

An inflammatory response accompanies the reversible pneumotoxicity caused by butylated hydroxytoluene (BHT) administration to mice. Lung tumor formation is promoted by BHT administration following an initiating agent in BALB/cByJ mice, but not in CXB4 mice. To assess the contribution of inflammation...

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Bibliographic Details
Published in:Toxicology (Amsterdam) 2001-12, Vol.169 (1), p.1-15
Main Authors: Bauer, Alison K, Dwyer-Nield, Lori D, Hankin, Joseph A, Murphy, Robert C, Malkinson, Alvin M
Format: Article
Language:English
Subjects:
6-Ketoprostaglandin F1 alpha - biosynthesis
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Antioxidants - pharmacology
Antioxidants - toxicity
Aspirin - pharmacology
Biological and medical sciences
Bronchoalveolar lavage
Bronchoalveolar Lavage Fluid - chemistry
Butylated Hydroxytoluene - pharmacology
Butylated Hydroxytoluene - toxicity
Carcinogenesis, carcinogens and anticarcinogens
Carcinogens - pharmacology
Carcinogens - toxicity
Chemical agents
Chronic inflammation
Cyclooxygenase
Cyclooxygenase 1
Cyclooxygenase 2
Dinoprostone - biosynthesis
Immunoblotting
Immunoenzyme Techniques
Immunohistochemistry
Isoenzymes - biosynthesis
Lung - drug effects
Lung - enzymology
Lung - pathology
Lung Neoplasms - chemically induced
Lung Neoplasms - pathology
Male
Medical sciences
Membrane Proteins
Mice
Mice, Inbred BALB C
Pneumonia - chemically induced
Pneumonia - metabolism
Pneumonia - pathology
Prostaglandin-Endoperoxide Synthases - biosynthesis
Prostaglandins
Statistics, Nonparametric
Strain differences
Tumors
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Summary:An inflammatory response accompanies the reversible pneumotoxicity caused by butylated hydroxytoluene (BHT) administration to mice. Lung tumor formation is promoted by BHT administration following an initiating agent in BALB/cByJ mice, but not in CXB4 mice. To assess the contribution of inflammation to this differential susceptibility, we quantitatively characterized inflammation after one 150 mg/kg body weight, followed by three weekly 200 mg/kg ip injections of BHT into male mice of both strains. This examination included inflammatory cell infiltrate and protein contents in bronchoalveolar lavage (BAL) fluid, cyclooxygenase (COX)-1 and COX-2 expression in lung extracts, and PGE 2 and PGI 2 production by isolated bronchiolar Clara cells. BAL macrophage and lymphocyte numbers increased in BALB mice ( P
ISSN:0300-483X
1879-3185
DOI:10.1016/S0300-483X(01)00475-9