Effect of methimazole on rat renal carcinogenesis induced by N-ethyl-N-hydroxyethylnitrosamine.
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.
Konishi
N
N
Second Department of Pathology, Nara Medical University, Japan.
Kitamura
M
M
Hayashi
I
I
Matsuda
H
H
Tao
M
M
Naitoh
H
H
Kitahori
Y
Y
Hiasa
Y
Y
D000236:Adenoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002114:Calcinosis / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity*; D004052:Diethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008713:Methimazole / Q000494:pharmacology*; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D016588:Anticarcinogenic Agents; D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; D002273:Carcinogens; C023845:N-ethyl-N-hydroxyethylnitrosamine; D004052:Diethylnitrosamine; D008713:Methimazole; D001973:Bromodeoxyuridine