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Toxicologic Pathology
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Evaluation of Carcinogenic Responses in the Eker Rat following Short-Term Exposure to Selected Nephrotoxins and Carcinogens

Laura Dill Morton

Pharmacia Corporation, Skokie, Illinois 60077, laura.dill.morton{at}pharmacia.com

Ashraf F. Youssef

Pharmacia Corporation, Skokie, Illinois 60077

Eric Lloyd

Pharmacia Corporation, Skokie, Illinois 60077

Anthony L. Kiorpes

Primedica Redfield, Redfield, Arkansas 72132

Thomas L. Goldsworthy

Integrated Laboratory Systems, Inc, Research Triangle Park, North Carolina 27709

Farrel L. Fort

Pharmacia Corporation, Skokie, Illinois 60077

This study examined the response of the Eker rat to nephrotoxic compounds and to genotoxic nonrenal carcinogens. Groups of male Eker rats received either no treatment; a vehicle treatment; treatment with a noncarcinogeni c nephrotoxin (aluminum nitrilotriacetate, 2 mg/kg/day of aluminum, intraperitoneally, 3 days per week or cyclosporine A, 30 mg/kg/day, orally by gavage, 7 days/week); or treatment with a genotoxic nonrenal carcinogen (furan, 8 mg/kg/day, orally by gavage, 5 days/week or 2,4-diaminotoluene, 6.5 mg/kg/day, orally by gavage, 7 days/week or 2-nitropropane, 89 mg/kg/day, orally by gavage, 3 days/week). Duration of treatment was 4 and/or 6 months. Tissues from the Eker rats were evaluated microscopically and numbers of proliferative renal lesions were counted. Administration of nephrotoxic compounds (Al-NTA and cyclosporine) significantly increased the number of preneoplasti c and neoplasti c renal lesions in the Eker rat compared to concurrent vehicle controls. The genotoxi c nonrenal carcinogens had no consistent effect on numbers of preneoplastic or neoplastic renal lesions and did not produce neoplasms in the expected target organ (liver).

Key Words: Eker • carcinogenesis • alternative model • rat • bioassay.

Toxicologic Pathology, Vol. 30, No. 5, 559-564 (2002)
DOI: 10.1080/01926230290105794
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