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Title: Perinatal radiation-induced renal damage in the beagle

Abstract

The developing perinatal kidney is particularly sensitive to radiation. The pathogenesis of the radiation-induced lesion is related to the destruction of outer cortical developing nephrons and direct radiation injury with secondary hemodynamic alterations in remnant nephrons. In this study, which is part of a life span investigation of the effects of whole-body gamma radiation during prenatal and early postnatal life, dogs were given 0, 0.16, 0.83, or 1.25 Gy irradiation at either 55 days postcoitus or 2 days postpartum and were examined morphometrically and histopathologically at 70 days of age. Although irradiated dogs showed no reduction in the total number of nephrons per kidney, there was a significant increase in the total number and relative percentage of immature, dysplastic glomeruli. In addition, deeper cortical glomeruli of irradiated kidneys exhibited mesangial sclerosis similar to that associated with progressive renal failure in our previous studies. These findings are in accord with those reported at doses of 2.24 to 3.57 Gy and demonstrate that the perinatal kidney is affected by radiation doses much lower than previously demonstrated.

Authors:
;  [1]
  1. (Colorado State Univ., Fort Collins (USA))
Publication Date:
OSTI Identifier:
7006157
Resource Type:
Journal Article
Resource Relation:
Journal Name: Radiation Research; (USA); Journal Volume: 122:1
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; KIDNEYS; BIOLOGICAL RADIATION EFFECTS; BEAGLES; GAMMA RADIATION; LIFE SPAN; NEONATES; NERVE CELLS; PRENATAL IRRADIATION; RADIATION DOSES; WHOLE-BODY IRRADIATION; ANIMAL CELLS; ANIMALS; BIOLOGICAL EFFECTS; BODY; DOGS; DOSES; ELECTROMAGNETIC RADIATION; EXTERNAL IRRADIATION; IONIZING RADIATIONS; IRRADIATION; MAMMALS; ORGANS; PRENATAL EXPOSURE; RADIATION EFFECTS; RADIATIONS; SOMATIC CELLS; VERTEBRATES; 560152* - Radiation Effects on Animals- Animals

Citation Formats

Jaenke, R.S., and Angleton, G.M. Perinatal radiation-induced renal damage in the beagle. United States: N. p., 1990. Web. doi:10.2307/3577583.
Jaenke, R.S., & Angleton, G.M. Perinatal radiation-induced renal damage in the beagle. United States. doi:10.2307/3577583.
Jaenke, R.S., and Angleton, G.M. Sun . "Perinatal radiation-induced renal damage in the beagle". United States. doi:10.2307/3577583.
@article{osti_7006157,
title = {Perinatal radiation-induced renal damage in the beagle},
author = {Jaenke, R.S. and Angleton, G.M.},
abstractNote = {The developing perinatal kidney is particularly sensitive to radiation. The pathogenesis of the radiation-induced lesion is related to the destruction of outer cortical developing nephrons and direct radiation injury with secondary hemodynamic alterations in remnant nephrons. In this study, which is part of a life span investigation of the effects of whole-body gamma radiation during prenatal and early postnatal life, dogs were given 0, 0.16, 0.83, or 1.25 Gy irradiation at either 55 days postcoitus or 2 days postpartum and were examined morphometrically and histopathologically at 70 days of age. Although irradiated dogs showed no reduction in the total number of nephrons per kidney, there was a significant increase in the total number and relative percentage of immature, dysplastic glomeruli. In addition, deeper cortical glomeruli of irradiated kidneys exhibited mesangial sclerosis similar to that associated with progressive renal failure in our previous studies. These findings are in accord with those reported at doses of 2.24 to 3.57 Gy and demonstrate that the perinatal kidney is affected by radiation doses much lower than previously demonstrated.},
doi = {10.2307/3577583},
journal = {Radiation Research; (USA)},
number = ,
volume = 122:1,
place = {United States},
year = {Sun Apr 01 00:00:00 EST 1990},
month = {Sun Apr 01 00:00:00 EST 1990}
}
  • Bilateral, whole-body /sup 60/Co ..gamma.. radiation (270 to 435 R) of beagles at 55 days in utero or 2 days of age resulted in a loss of kidney mass which was associated with thinning of the renal cortex and the presence of numerous immature glomeruli and nests of degenerating cells. Morphometric examination demonstrated a decrease in the density of mature and total glomeruli. These findings suggest that as a result of perinatal irradiation a significant reduction in structural and functional renal mass occurs which is due to a destruction of primitive metanephric tissue and an arrest in the further maturationmore » of some nephrons. These events are associated with life-threatening secondary renal lesions which are characterized by progressive mesangial sclerosis of glomeruli and chronic renal failure.« less
  • The renal effects of whole body irradiation in the perinatal period were studied in the dog. Ninety-three dogs received a single sublethal exposure in the range of 270 to 435 R in either late gestation (55 days postcoitus) or early postnatal life (2 days postpartum) and were sacrificed at 70 days, 2, or 4 years of age. Early renal lesions in 70-day-old irradiated dogs were characterized by arrested glomerular maturation and degeneration resulting in reduced functional renal mass. Mature glomeruli exhibited mesangial proliferation. At 2 and 4 years of age, surviving irradiated dogs exhibited sever renal disease associated with progressivemore » glomerular damage which was characterized by mesangial proliferation and compression of capillary lumina, epithelial degeneration and focal capsular adhesions, and ultimately obliterative glomerulosclerosis. Twenty-one of the 93 irradiated dogs died in renal failure before 4 years of age with advanced glomerulosclerosis. The phatogenesis of this progressive renal lesion may be related to the interaction of three specific factors. These include (1) the effect of direct radiation damage to mature kidney components; (2) the loss of outer cortical nephrons resulting in increased work load of the surviving nephrons; and (3) the effect of compensatory hypertrophy related to the loss of renal parenchyma as the rapid growth rates associated with kidney maturation.« less
  • The response of mouse kidneys to multifraction irradiation was assessed using three nondestructive functional end points. A series of schedules was investigated giving 1, 2, 4, 8, 16, 32, or 64 equal X-ray doses, using doses per fraction in the range of 0.9 to 16 Gy. The overall treatment time was kept constant at 3 weeks. Kidney function was assessed from 19 to 48 weeks after irradiation by measuring changes in isotope clearance, urine output, and hematocrit. All three assays yielded steep dose-effect curves from which the repair capacity of kidney could be estimated by comparing the isoeffective doses inmore » different schedules. There was a marked influence of fractionation, with increasing dose being required to achieve the same level of damage for increasing fraction number, even between 32 and 64 fractions. The data are well fitted by a linear quadratic dose-response equation, and analysis of the data would suggest that hyperfractionation, using extremely small X-ray doses per fraction, would spare kidneys relative to tumors and acutely responding tissues.« less
  • Two nondestrutive assays of functional impairment were developed to measure renal damage in mice after local irradiation of both kidneys with 240-kV X rays. Daily urine output after irradiation was measured indirectly by determining urination frequency. A dose-related response began 17 weeks after treatment and then progressed; dose-response curves with a threshold of 12 Gy were established by 22 weeks. The time of onset of damage was dose related and there was some recovery of kidney function between 25 and 38 weeks. The rate of excretion of /sup 51/Cr-EDTA was measured as an estimate of glomerular filtration either by sequentialmore » external counting over 20 min or from the activity remaining in a single blood sample at 60 min. Both methods gave dose-response curves, but the results from the blood sample were more precise. These assays are suitable for sequential testing of individual mice and have been used to establish a dose-related latent period of approximately 17 weeks after bilateral renal irradiation.« less
  • As part of a long-term study to evaluate health effects of pre- and postnatal irradiation, dental development was examined. Beagles were irradiated in utero at 8, 28, or 55 days postcoitus or postnatally at 2, 70, or 365 days postpartum. Whole-body /sup 60/Co gamma radiation doses ranged from 0 to 3.8 Gy. There was an age-dependent dose-related increase in premolar hypodontia for animals irradiated at 55 days postcoitus or 2 days postpartum with doses of 0.83 Gy or higher and for those irradiated at 28 days postcoitus with 1.2 Gy or higher.