Radiation-induced fibrosis: the structure/function relationship.

Abstract

Fibrosis is a frequent complication of therapeutic radiation delivered to organ sites such as the thorax and pelvic region. We investigated the relationship between function, and biochemical and structural changes in the lung and colon of CBA mice irradiated with 240 kV X-rays. Progressive changes in lung function, as evidenced by increased breathing rates were observed out to 6 months post-irradiation. Biochemical studies demonstrated increased metabolism (synthesis and breakdown) of collagen around 6 months after irradiation, but provided no evidence of net collagen accumulation. Analysis of collagen isotypes revealed a slight increase in the ratio of types I and III. In the colons of irradiated mice, there was a progressive decrease in compliance out to 14 months post-irradiation. Collagen and total protein synthesis and breakdown rates were increased at early times, and returned to control levels by 4 months. No net accumulation of collagen was observed at any time. The ratio of collagen type I to III was increased at one year post-irradiation. We conclude that, in the CBA mouse, late functional changes after X-irradiation are not the result of a build-up of excessive connective tissue, although changes in collagen metabolism may occur relatively early on in the response to radiation.