NCI-Black-Reiter (NBR) male rats fail to develop renal disease following exposure to agents that induce alpha-2u-globulin (alpha 2u) nephropathy.
The NCI-Black-Reiter (NBR) rat is the only strain of male rat known not to synthesize the hepatic form of the low molecular weight protein, alpha 2u-globulin. In previous studies, NBR rats were shown not to develop renal disease when exposed to decalin, a compound known to induce alpha 2u-globulin nephropathy in other rat strains. The objective of this study was to show that the presence of alpha 2u-globulin (alpha 2u) is essential for the development of this syndrome in rats exposed to 2,2,4-trimethylpentane (TMP), 1,4-dichlorobenzene (DCB), isophorone (IP), PS-6 unleaded gasoline (UG), and d-limonene (d-L). The induction of alpha 2u-nephropathy in F344 male rats with lindane was used as a positive control and this response was contrasted to male NBR and female F344 rats treated with lindane. Five to seven 11-week-old male NBR rats 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 female F344 rats were exposed to lindane (10 mg/kg/day) by oral gavage on 4 consecutive days. NBR male and F344 male and female rats gavaged with corn oil were incorporated in the study as vehicle controls. The presence of hyaline droplets was assessed in perfusion-fixed kidneys by staining paraffin sections with Mallory-Heidenhein stain and in GMA sections with Lee's methylene basic blue fuchsin stain. Paraffin sections were also analyzed immunohistochemically for the presence of alpha 2u. Under exposure conditions that clearly induce alpha 2u-nephropathy in male F344 rats, no lesions, hyaline droplets, or alpha 2u were detectable in treated or control male NBR and female F344 rats. It is thus concluded that the presence of alpha 2u is causal to the development of renal disease in rats exposed to TMP, DCB, IP, UG, d-L, and lindane.
Dietrich
D R
DR
Department of Environmental Sciences, University of North Carolina, Chapel Hill 27599.
Swenberg
J A
JA
D000510:Alpha-Globulins / Q000096:biosynthesis*; D000818:Animals; D008401:Gas Chromatography-Mass Spectrometry; D015386:Hazardous Substances / Q000633:toxicity; D001556:Hexachlorocyclohexane / Q000633:toxicity; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D008297:Male; D008970:Molecular Weight; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains
D000510:Alpha-Globulins; D015386:Hazardous Substances; C013803:alpha 2u globulin; D001556:Hexachlorocyclohexane