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Toxicologic Pathology
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Journal Article

Effect of Hexachloro-1,3-butadiene on Renal Carcinogenesis in Male Rats Pretreated with N-Ethyl-N-hydroxyethylnitrosamine

Yoshinori Nakagawa

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

Yoshiteru Kitahori

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

Masaki Cho

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

Noboru Konishi

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

Ken-Ichi Tsumatani

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

Seiichiro Ozono

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

Eigoro Okajima

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

Yoshihiko Hirao

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

Yoshio Hiasa

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

Hexachloro-1,3-butadiene (HCBD) is a potent nephrotoxicant that selectively damages the straight portion (pars recta) of the proximal tubule in the rat. To determine its effects on carcinogenesis, HCBD was administered for 30 wk at a concentration of 0.1% by weight in basal diet to male Wistar rats previously given 0.1% Af-ethyl-W-hydroxyethylnitrosamine (EHEN) in the drinking water for 2 wk. The combined treatment resulted in a significantly higher incidence of renal cell tumors than when EHEN was administered alone. This chronic exposure and a short course of a 0.2% HCBD diet for 3 wk caused marked increase in the numbers of bromo-deoxyuridine-incorporating cells or proliferating cell nuclear antigen-positive cells in the outer stripe of the kidney. The ability of HCBD to promote EHEN-initiated renal tumorigenesis in rats thus appears to be associated intimately with linked nephropathy and subsequent cell proliferation.

Key Words: Hexachloro-1,3-butadiene (HCBD) • N-ethyl-W-hydroxyethylnitrosamine (EHEN) • renal carcinogenesis • nephrotoxin

Toxicologic Pathology, Vol. 26, No. 3, 361-366 (1998)
DOI: 10.1177/019262339802600309
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