Radiation-induced XXXX : a role for chronic oxidative stress?

@entity8 @entity82 @entity7599 @entity26 @entity1808 @entity3202 @entity1463 @entity194 @entity35 @entity631 @entity10340
Kidney irradiation clearly leads to a progressive reduction in function associated with concomitant @entity631 and/or tubulointerstitial @entity82 . However, the particular cell types, mediators and/or mechanisms involved in the development and progression of radiation @entity8 remain ill defined. @entity1808 ( @entity1808 ) plays a major pathogenic role; administration of @entity1808 blockers markedly abrogates the severity of radiation @entity8 in experimental models. Both ionizing radiation and @entity10340 II signal via generation of reactive @entity26 species (ROS). Thus, we hypothesized that localized kidney irradiation might lead to a chronic oxidative stress. In view of the difficulty in measuring ROS in vivo we adopted an indirect immunohistochemical approach in which we used a monoclonal antibody specific for @entity7599 ( @entity7599 ), one of the most commonly used markers of DNA oxidation. The right kidney of 7-8 week-old male @entity35 was removed. Five to 6 weeks later the remaining hypertrophied kidney was irradiated with single doses of 0-20.0 Gy X-rays. Groups of @entity35 , three per dose, were killed at 4, 8, 16 and 24 weeks post-irradiation, their kidneys fixed, and sections stained with the @entity7599 -specific antibody N45.1. For quantitation of glomerular DNA oxidation with the N45.1 antibody stained sections, 50 glomeruli/animal were counted. The presence of any intensely stained nuclei within the glomerular tuft was scored as positive. Quantitation of tubular DNA oxidation employed a 10 x 10 point ocular grid. Sections were examined at 400 magnification; 250 tubular profiles were counted. All tubules with any nuclear staining were scored as positive.Sham-irradiated kidneys showed little evidence of DNA oxidation over the experimental period. In contrast, localized kidney irradiation led to a marked, dose-independent increase in glomerular and tubular cell nuclear DNA oxidation. This increase was evident at the first time point studied, i.e. 4 weeks after irradiation, and persisted for up to 24 weeks postirradiation. DNA oxidation in the irradiated kidney was only seen in apparently viable glomerular and tubular cells. Thus, while from 16 to 24 weeks post-irradiation structural alterations had progressed to @entity8 and @entity194 , positive staining for @entity7599 was not observed in severely @entity3202 tubules. Similarly, fewer positive staining cells were noted in glomeruli undergoing @entity1463 , while none were seen in totally sclerotic glomeruli. These data support the hypothesis that renal irradiation is associated with a chronic and persistent oxidative stress.
