Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1993 Dec;101(Suppl 5):281–285. doi: 10.1289/ehp.93101s5281

Retrospective study of possible alpha-2 mu-globulin nephropathy and associated cell proliferation in male Fischer 344 rats dosed with t-butyl alcohol.

K Takahashi 1, C Lindamood 3rd 1, R R Maronpot 1
PMCID: PMC1519457  PMID: 7516874

Abstract

Tert-butyl alcohol, an important commodity chemical, additive to unleaded gasoline, and contaminant of drinking water, was evaluated for toxicity and was found to enhance nephropathy in male Fischer 344 rats. Because male rats treated with t-butyl alcohol for 2 years had a low incidence of renal cortical tumors, additional renal sections for the 90-day toxicity study were examined for the presence of hyaline droplet accumulation, nephropathy, and evidence of replicative DNA synthesis (S-phase nuclei) to indirectly and retrospectively investigate a possible role of alpha-2 mu-globulin in the pathogenesis of the nephropathy. Dose levels for t-butyl alcohol were 0, 0.25, 0.5, 1, 2, and 4% (w/v) administered in drinking water. Significant body weight gain depressions were observed in all treated males, and there was an absolute weight loss in the 4% male group, none of which survived to the end of the study. Except for the 4% dose group, there was a treatment-related increase in hyaline droplet accumulation in the renal proximal tubules with crystalline, rectangular, and rhomboid forms of the protein evident. The severity of nephropathy was enhanced in treated rats, except for the 4% dose group. Replicative DNA synthesis, as measured by immunohistochemical staining for proliferating cell nuclear antigen, was increased in proximal tubules of rats dosed with 2% t-butyl alcohol. It is concluded that t-butyl alcohol exacerbated nephropathy in male Fischer 344 rats and increased renal accumulation of hyaline protein material consistent with alpha-2 mu-globulin deposition.

Full text

PDF
282

Images in this article

283FIGURE 2.
on p.283
283FIGURE 3.
on p.283
284FIGURE 4.
on p.284
284FIGURE 5.
on p.284
284FIGURE 7.
on p.284

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bauer G. A., Burgers P. M. The yeast analog of mammalian cyclin/proliferating-cell nuclear antigen interacts with mammalian DNA polymerase delta. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7506–7510. doi: 10.1073/pnas.85.20.7506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bravo R., Frank R., Blundell P. A., Macdonald-Bravo H. Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature. 1987 Apr 2;326(6112):515–517. doi: 10.1038/326515a0. [DOI] [PubMed] [Google Scholar]
  3. Celis J. E., Celis A. Cell cycle-dependent variations in the distribution of the nuclear protein cyclin proliferating cell nuclear antigen in cultured cells: subdivision of S phase. Proc Natl Acad Sci U S A. 1985 May;82(10):3262–3266. doi: 10.1073/pnas.82.10.3262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Celis J. E., Madsen P., Celis A., Nielsen H. V., Gesser B. Cyclin (PCNA, auxiliary protein of DNA polymerase delta) is a central component of the pathway(s) leading to DNA replication and cell division. FEBS Lett. 1987 Aug 10;220(1):1–7. doi: 10.1016/0014-5793(87)80865-7. [DOI] [PubMed] [Google Scholar]
  5. Dietrich D. R., Swenberg J. A. NCI-Black-Reiter (NBR) male rats fail to develop renal disease following exposure to agents that induce alpha-2u-globulin (alpha 2u) nephropathy. Fundam Appl Toxicol. 1991 May;16(4):749–762. doi: 10.1016/0272-0590(91)90161-v. [DOI] [PubMed] [Google Scholar]
  6. Dietrich D. R., Swenberg J. A. The presence of alpha 2u-globulin is necessary for d-limonene promotion of male rat kidney tumors. Cancer Res. 1991 Jul 1;51(13):3512–3521. [PubMed] [Google Scholar]
  7. Goldsworthy T. L., Lyght O., Burnett V. L., Popp J. A. Potential role of alpha-2 mu-globulin, protein droplet accumulation, and cell replication in the renal carcinogenicity of rats exposed to trichloroethylene, perchloroethylene, and pentachloroethane. Toxicol Appl Pharmacol. 1988 Nov;96(2):367–379. doi: 10.1016/0041-008x(88)90095-6. [DOI] [PubMed] [Google Scholar]
  8. Greenwell A., Foley J. F., Maronpot R. R. An enhancement method for immunohistochemical staining of proliferating cell nuclear antigen in archival rodent tissues. Cancer Lett. 1991 Sep;59(3):251–256. doi: 10.1016/0304-3835(91)90149-c. [DOI] [PubMed] [Google Scholar]
  9. Kurki P., Vanderlaan M., Dolbeare F., Gray J., Tan E. M. Expression of proliferating cell nuclear antigen (PCNA)/cyclin during the cell cycle. Exp Cell Res. 1986 Sep;166(1):209–219. doi: 10.1016/0014-4827(86)90520-3. [DOI] [PubMed] [Google Scholar]
  10. Lindamood C., 3rd, Farnell D. R., Giles H. D., Prejean J. D., Collins J. J., Takahashi K., Maronpot R. R. Subchronic toxicity studies of t-butyl alcohol in rats and mice. Fundam Appl Toxicol. 1992 Jul;19(1):91–100. doi: 10.1016/0272-0590(92)90032-d. [DOI] [PubMed] [Google Scholar]
  11. Short B. G., Burnett V. L., Cox M. G., Bus J. S., Swenberg J. A. Site-specific renal cytotoxicity and cell proliferation in male rats exposed to petroleum hydrocarbons. Lab Invest. 1987 Nov;57(5):564–577. [PubMed] [Google Scholar]
  12. Swenberg J. A., Short B., Borghoff S., Strasser J., Charbonneau M. The comparative pathobiology of alpha 2u-globulin nephropathy. Toxicol Appl Pharmacol. 1989 Jan;97(1):35–46. doi: 10.1016/0041-008x(89)90053-7. [DOI] [PubMed] [Google Scholar]
  13. Takasaki Y., Deng J. S., Tan E. M. A nuclear antigen associated with cell proliferation and blast transformation. J Exp Med. 1981 Dec 1;154(6):1899–1909. doi: 10.1084/jem.154.6.1899. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES