Beagle dogs were exposed by inhalation to an aerosol of <tex-math>${}^{144}{\rm Ce}$</tex-math> clay to quantitate the relationship between pulmonary radiation dose and induced fibrosis. Collagen, elastin, glucosamine and the ratios of elastin/collagen, hydroxyproline/hydroxylysine and hydroxyproline/proline were determined to indicate changes in connective tissue constituents. Total lung collagen was partitioned into native collagen, soluble collagen and ultrafilterable hydroxyproline peptides. Increased total lung collagen correlated best with increasing cumulative radiation dose and increasing time after inhalation exposure. The increase in total lung collagen was not seen until more than 4 mo after exposure and a cumulative dose of about 40,000 rad. Soluble collagen and low molecular weight hydroxyproline peptide quantities both increased at 2 mo after exposure and cumulative doses of 20,000-27,000 rad. A variable elastin response apparently was not related to either increasing time or increasing radiation dose after exposure. These results indicate that collagen accumulation is an important factor in pulmonary fibrosis. Although collagen synthesis and breakdown were both activated at a relatively early time after inhalation, a significant increase in native collagen (scarring) occurred only when the metabolic balance was altered by protracted time or irradiation after exposure. The interrelationships observed in this study provide insight into the mechanism of fibrosis induced by chronic pulmonary injury.

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