Pulmonary fibrosis: a possible mechanism
The hypothesis that pulmonary fibrosis, a chronic and incurable respiratory disease in man, could develop if reepithelialization following acute lung damage was compromised by a second toxic agent was investigated. Previous work suggested that in the lung dividing alveolar type II cells are more susceptible to the cytotoxic effect of oxygen than dividing interstitial cells. Male BALB/c mice were injected ip with 400 mg/kg butylated hydroxytoluene (BHT) and placed immediately in 70% oxygen or air for 6 days. In vivo incorporation of thymidine into pulmonary DNA was significantly inhibited by exposure to oxygen 2 and 4 days after BHT alone. Animals exposed to oxygen following BHT developed extensive interstitial fibrosis by Day 14, as determined by both hydroxyproline analysis and histopathological examination. No fibrosis developed in mice treated with oxygen alone or when oxygen treatment was delayed until 7 days following BHT injection. Mice treated with BHT alone showed only slight lung fibrosis. The minimum length of exposure to oxygen resulting in increased lung hydroxyproline was 24 h. Pretreatment for 7 days with oxygen, followed by BHT, did not enhance the development of fibrosis. The combined effects of BHT and oxygen, when given in the correct temporal sequence, were synergistic and not simply additive. We concluded that pulmonary fibrosis can result from interaction between an agent causing acute lung damage and a second toxic agent which comprises reepithelialization.
- Research Organization:
- Oak Ridge National Lab., TN
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 6354350
- Journal Information:
- Toxicol. Appl. Pharmacol.; (United States), Vol. 51
- Country of Publication:
- United States
- Language:
- English
Similar Records
Pathogenic mechanism in lung fibrosis. [Synergistic effects of BHT, O/sub 2/, and x rays in mice]
Role of toxicological interactions in lung injury
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANTIOXIDANTS
TOXICITY
EPITHELIUM
SENSITIVITY
LUNGS
OXYGEN
CELL PROLIFERATION
DNA
FIBROSIS
HYDROXY COMPOUNDS
MICE
RESPONSE MODIFYING FACTORS
THYMIDINE
TIME DEPENDENCE
TOLUENE
ANIMAL TISSUES
ANIMALS
AROMATICS
AZINES
BODY
ELEMENTS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
MAMMALS
NONMETALS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PYRIMIDINES
RESPIRATORY SYSTEM
RIBOSIDES
RODENTS
TISSUES
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550900 - Pathology