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Toxicologic Pathology
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Journal Article

Effect of Methimazole on Rat Renal Carcinogenesis Induced by N-Ethyl-N-Hydroxyethylnitrosamine

Noboru Konishi

Second Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan

Motokazu Kitamura

Second Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan

Isao Hayashi

Second Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan

Hirofumi Matsuda

Second Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan

Ming Tao

Second Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan

Hiroaki Naitoh

Second Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan

Yoshiteru Kitahori

Second Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan

Yoshio Hiasa

Second Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan

The effect of methimazole on N- ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal lesions was investigated in a medium-term initiation/promotion bioassay in male Wistar rats. EHEN-initiated rats underwent unilateral nephrectomy of the left kidney and subsequent addition of the renal tumor promoters trisodium nitrilotriacetate (NTA), potassium dibasic phosphate (PDP), or hydroquinone (HQ), alone or in combination with methimazole, to the diet for 20 wk. The addition of methimazole reduced the severity of simple and adenomatous renal hyperplasias induced by NTA, PDP, and HQ, but had no effect on the number of renal cell tumors that arose in EHEN + NTA groups. Methimazole also decreased the bromodeoxyuridine (BrdU) labeling indices, but had little effect on the expression of {alpha} 2u-globulin in treated kidneys as compared to controls. It appears that methimazole exhibits antagonistic properties to nongenotoxic nephrotoxins, protecting against renal damage but not against tumorigenesis, probably arising from genotoxic insult.

Key Words: Medium-term bioassay • nephrotoxicity • trisodium nitrilotriacetate • potassium dibasic phosphate • hydroquinone

Toxicologic Pathology, Vol. 23, No. 5, 606-611 (1995)
DOI: 10.1177/019262339502300506
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