Histopathology and Cell Proliferation Induced by 2,2,4-Trimethylpentane in the Male Rat Kidney

Toxicologic Pathology - Tập 14 Số 2 - Trang 194-203 - 1986
Brian Short1, Vicki L. Burnett1, James A. Swenberg1
1Department of Biochemical Toxicology and Pathobiology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.

Tóm tắt

Unleaded gasoline causes acute and chronic nephrotoxicity and renal tumors in male rats, but not female rats or mice of either sex. An active nephrotoxic component of unleaded gasoline has been identified as 2,2,4-trimethylpentane (TMP). The first objective of this study was to characterize light microscopic renal lesions induced in male F344 rats by a 21-day gavage regimen of 50 to 500 mg/kg TMP. The second objective was to localize and quantitate sites of renal cell proliferation induced by the same TMP dose regimens using histoautoradiographic analysis after [3H]thymidine incorporation. Light microscopic lesions in the proximal convoluted tubule consisted of protein droplet and crystalloid body accumulation, degeneration, and necrosis, and were similar to lesions noted in previous inhalation and gavage studies with other hydrocarbon compounds. The above renal lesions were not dose-related, although tubular dilation of thin limb segments with granular cell debris was dose-related. In cell proliferation studies TMP induced a non-dose-related five- to sixfold increase in the labelling index of the same proximal convoluted tubule portions (P2 segment) that contained severe crystalloid body accumulation, degeneration, and necrosis. Less pronounced, but statistically significant (p ≤ 0.05), increases in cell proliferation were also observed in other nephron segments, indicating a generalized regenerative response of the kidney to TMP. The cytotoxic and regenerative renal effects of TMP administered by gavage suggest that similar mechanisms may be involved in the induction of kidney tumors in male rats following chronic inhalation exposure to unleaded gasoline.

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Tài liệu tham khảo

Alden CL, 1984, Renal Effects of Petroleum Hydrocarbons, 107

10.3109/10520297609116677

3. Borriston Project Number 1707. (1984). Serial sacrifice with unleaded gasoline in rats. Light microscopy pathology summary. Experimental Pathology Laboratories, Inc.

Busey WM, 1984, Renal Effects of Petroleum Hydrocarbons, 57

Cain H, 1977, Virchows Arch. Abt. B Cell Pathol., 22, 55, 10.1007/BF02889206

Conaway CC, 1984, Applied Toxicology of Petroleum Hydrocarbons, 89

Cuppage FE, 1967, Am. J. Pathol., 51, 405

Cuppage FE, 1972, Lab. Invest., 26, 122

9. Doull J, Bridges BA, Kroes R, Golberg L, Munro IC, Paynter OE, Pitot HC, Squire R, Williams G, and Darby W (1983). The relevance of mouse liver hepatoma to human carcinogenic risk. A report of the International Expert Advisory Committee to the Nutrition Foundation. The Nutrition Foundation, Inc., Washington, D.C.

10.3109/10408447709003377

Haagsma BH, 1980, Br. J. Exp. Pathol., 61, 227

Halder CA, 1984, Renal Effects of Petroleum Hydrocarbons, 73

Hard GC, 1975, Cancer Res., 35, 3762

Kitchen DN, 1984, Renal Effects of Petroleum Hydrocarbons, 65

10.1128/AAC.24.4.586

10.1007/978-3-642-69132-4_91

MacFarland HN, 1984, Renal Effects of Petroleum Hydrocarbons, 51

10.1016/S0022-5320(66)80043-6

Maunsbach AB, 1973, Handbook of Physiology, Section 8: Renal Physiology, 31

10.1084/jem.99.6.589

Peto R, 1980, Long Term and Short Term Screening Assays for Carcinogenesis: A Critical Appraisal., 311

Phillips RD, 1984, Renal Effects of Petroleum Hydrocarbons, 89

10.1016/0378-4274(84)90128-0

10.1016/0041-008X(86)90207-3

10.1016/0304-4165(66)90477-6

Solleveld HA, 1984, J. Natl. Cancer Inst., 72, 929

27. Universities Associated for Research and Education in Pathology, Inc. (1984). Hydrocarbon toxicity: Acute, subchronic and chronic effects in relation to unleaded gasoline exposure of rodents with comments on significance to man. Contract No. PS-6 UAREP (504–2) with American Petroleum Institute.

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Toxicologic Pathology

Tập 14 Số 2

194-203

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