Radiation-induced changes in collagen isotypes I, III, and IV in the lung of LAF1 mouse: effects of time, dose, and WR-2721
Alterations in the amount and distribution of pulmonary connective tissue are commonly observed subsequent to thoracic radiotherapy. The extent to which these changes are important in the expression of radiation damage and its repair remains unclear. We have quantitated changes in the parenchymal levels of collagen types I, III, and IV in the lungs of LAF1 mice at intervals to 1 year, following doses of 0-14 Gy, 300 kV X rays, or 0-18 Gy in the presence of the radioprotective compound, WR-2721. The method of quantitation, which involves video image analysis of fluorescent antibody stained, cryostat tissue sections, provides both quantitative and morphological information for the three collagen isotypes. Type I collagen peaked in tissue content at 15 and 30 weeks postirradiation (p.i.), with transient return to control values 20-25 weeks p.i. Type III collagen peaked at 15 and 25 weeks p.i. and declined in tissue content at 20 and 30 weeks. Type IV peaked 15-20 weeks following irradiation, returned to control levels at 25 weeks, and reached a plateau above control values after 30 weeks. Fluctuations in collagen levels in the parenchyma were dose dependent but were not simultaneous, indicating a radiation response characterized by alpha-chain-specific regulation of collagen biosynthesis and breakdown. In general, WR-2721, which enhanced postirradiation survival (DMF, 1.3), reduced the magnitude and altered the timing of collagen fluctuations; again, the effects were type specific. The results clearly demonstrate that the postirradiation response of the connective tissue is dose dependent, is specific to each macromolecule, and involves both deposition and removal of extracellular matrix. These processes are independently influenced by the presence during irradiation of WR-2721.
- Research Organization:
- Cross Cancer Institute, Edmonton, Alberta (Canada)
- OSTI ID:
- 6865281
- Journal Information:
- Radiat. Res.; (United States), Vol. 115:3
- Country of Publication:
- United States
- Language:
- English
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COLLAGEN
BIOSYNTHESIS
LUNGS
DELAYED RADIATION EFFECTS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RADIOTHERAPY
SIDE EFFECTS
DOSE-RESPONSE RELATIONSHIPS
MICE
TIME DEPENDENCE
TISSUE DISTRIBUTION
X RADIATION
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
DISTRIBUTION
DRUGS
ELECTROMAGNETIC RADIATION
IONIZING RADIATIONS
MAMMALS
MEDICINE
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIATION EFFECTS
RADIATIONS
RADIOLOGY
RESPIRATORY SYSTEM
RODENTS
SCLEROPROTEINS
SYNTHESIS
THERAPY
VERTEBRATES
560152* - Radiation Effects on Animals- Animals