Evaluation of carcinogenic responses in the Eker rat following short-term exposure to selected nephrotoxins and carcinogens.
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 noncarcinogenic 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 preneoplastic and neoplastic renal lesions in the Eker rat compared to concurrent vehicle controls. The genotoxic 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).
Morton
Laura Dill
LD
Pharmacia Corporation, Skokie, Illinois 60077, USA. laura.dill.morton@pharmacia.com
Youssef
Ashraf F
AF
Lloyd
Eric
E
Kiorpes
Anthony L
AL
Goldsworthy
Thomas L
TL
Fort
Farrel L
FL
D000284:Administration, Oral; D000818:Animals; D030801:Animals, Genetically Modified; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity; D005663:Furans / Q000008:administration & dosage / Q000633:toxicity; D007274:Injections, Intraperitoneal; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D009571:Nitrilotriacetic Acid / Q000008:administration & dosage / Q000633:toxicity; D009595:Nitroparaffins / Q000008:administration & dosage / Q000633:toxicity; D010655:Phenylenediamines / Q000008:administration & dosage / Q000633:toxicity; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D011407:Propane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D005663:Furans; D009153:Mutagens; D009595:Nitroparaffins; D010655:Phenylenediamines; D016572:Cyclosporine; C016617:2-nitropropane; C010914:2,4-diaminotoluene; D009571:Nitrilotriacetic Acid; D011407:Propane; C039281:furan