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Radiation injury in the mouse kidney. I. Sequential light microscopic study

Journal Article · · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

A 1 year, sequential morphologic study of radiation-induced renal disease has been carried out in 260 mice. Both kidneys were irradiated locally, either with single doses (SD) (1100 to 1900 rad) or with 10 fractions over 9 elapsed days (total doses of 3500 to 5000 rad). The most striking alterations occurred in glomeruli and consisted of progressive replacement of capillary walls and capillary lumina by an acidophilic, periodic acid-Schiff (PAS)-positive material, containing basement-membrane fragments. These lesions appeared initially at 3 months, and increased in both degree and extent as a function of time. Tubular atrophy and stromal fibrosis was not seen before 4 months, and, although progressive, they did not reach the severity of the glomerular damage. Lesions of vessels larger than capillaries were extremely rare even at the end of observation (12 months) when glomeruli were already totally obliterated. In both fractionated and single dose studies, the lesions progressed with time. The survival of the SD mice was directly related to dose and time of observation; none of the mice receiving 1900 rad SD survived beyond 10 months, while 90 percent of those receiving 1100 rad SD were alive at 12 months. Although available data are not sufficient to determine the initial site(s) of radiation injury in the renal parenchyma, this light microscopic study and preliminary electron microscopic observations suggest that at least some of the initial lesions occur in glomeruli. The late lesions in the glomeruli of these mice are identical to those seen in specimens of humans with advanced radiation nephropathy. The murine model thus appears to be appropriate for the study of the pathogenesis of this condition.

Research Organization:
Stanford Univ. School of Medicine, CA
OSTI ID:
5111432
Journal Information:
Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 2:9/10; ISSN IOBPD
Country of Publication:
United States
Language:
English