Increased collagen and fluid content of mouse kidneys at 9 months after single or fractionated X irradiation.

Mouse kidneys have been analyzed at sacrifice, 9 months after single-dose and fractionated irradiation, using wet and dry weight, a biochemical determination of hydroxyproline, and quantitation of dilated renal tubules in histological preparations. Dose-response curves have been constructed to determine the sensitivity and precision of the assays and to study the influence of dose fractionation on a variety of radiation responses of the kidney. There was a marked loss of kidney weight, measured either wet or dry, with maximum changes from control values by factors of 3 and 5, respectively. The wet:dry weight ratio increased with X-ray dose, indicating that relative fluid content was increased even 9 months after irradiation. This could be partly attributed to dilated renal tubules. Total collagen content per kidney, determined by a hydroxyproline assay, showed a less marked dose dependence, with a maximum increase of a factor of 1.4. However, hydroxyproline per dry weight increased by a factor of 7, and this ratio proved to be the most sensitive and precise measure of radiation damage. The "fibrosis" that is detected in histological sections appears to be more a relative than an absolute alteration in connective tissue. The loss of parenchymal cell mass, particularly in the proximal tubules, is the predominant factor; the increase in the absolute amount of collagen per kidney contributes to a lesser degree. The influence of radiation dose fractionation was analyzed using a linear-quadratic response model. The alpha/beta ratios were between 0.9 and 2.9 Gy.