NCI-Black-Reiter (NBR) Male Rats Fail to Develop Renal Disease following Exposure to Agents That Induce {alpha}-2u-Globulin ({alpha}2u) Nephropathy

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, 749–762. 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.