NCI-Black-Reiter (NBR) Male Rats Fail to Develop Renal Disease following Exposure to Agents That Induce {alpha}-2u-Globulin ({alpha}2u) Nephropathy |
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Authors: | DIETRICH, D. R. SWENBERG, J. A. |
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Affiliation: | Departments of Environmental Sciences and Engineering and Pathology, University of North Carolina Chapel Hill, North Carolina 27599 Received July 30, 1990; accepted December 20, 1990 |
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Abstract: | NCI-Black-Reiler (NBR) Male Rats Fail to Develop Renal Diseasefollowing Exposure to Agents That Induce 2u-Globulin (2u) Nephropathy.Dietrich, D. R., and Swenberg, J. A. (1991). Fundam. Appl. Toxicol16, 749762. The NCI-Black-Reiter (NBR) rat is the onlystrain of male rat known not to synthesize the hepatic formof the low molecular weight protein, 2u-globulin. In previousstudies, NBR rats were shown not to develop renal disease whenexposed to decalin, a compound known to induce 2u-globulin nephropathyin other rat strains. The objective of this study was to showthat the presence of 2u-globulin (2u-) is essential for thedevelopment of this syndrome in rats exposed to 2,2,4-trimethylpentane(TMP), 1,4-dichlorobenzene (DCB), isopho-rone (IP), PS-6 unleadedgasoline (UG), and d-limonene (d-L). The induction of 2u-nephropathyin F344 male rats with lindane was used as a positive controland this response was contrasted to male NBR and female F344rats treated with lindane. Five to seven 11-week-old male NBRrats were exposed to TMP (500 mg/kg/day), DCB (500 mg/kg/day),IP (1000 mg/kg/day), UG (500 mg/kg/day), d-L (1650 mg/kg/day),or lindane (10 mg/kg/day) and five 11-week-old male and femaleF344 rats were exposed to lindane (10 mg/kg/day) by oral gavageon 4 consecutive days. NBR male and F344 male and female ratsgavaged with corn oil were incorporated in the study as vehiclecontrols. The presence of hyaline droplets was assessed in perfusion-fixedkidneys by staining paraffin sections with Mallory-Heidenheinstain and in GMA sections with Lee's methylene basic blue fuchsinstain. Paraffin sections were also analyzed immunohistochemicallyfor the presence of 2u-. Under exposure conditions that clearlyinduce 2u-nephropathy in male F344 rats, no lesions, hyalinedroplets, or 2u- were detectable in treated or control maleNBR and female F344 rats. It is thus concluded that the presenceof 2u is causal to the development of renal disease in ratsexposed to TMP, DCB, IP, UG, d-L, and lindane. |
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