Carcinogenic activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine in rats administered bis(2-hydroxypropyl)amine and sodium nitrite |
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Authors: | Yamamoto Kazuhiko; Nakajima Akira; Eimoto Hiroyuki; Tsutsumi Masahiro; Maruyama Hiroshi; Denda Ayumi; Nii Hiroaki; Mori Yukio; Konishi Yoichi |
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Institution: | Department of Oncological Pathology, Cancer Center, Nara Medical College 840 Shijo-cho, Kashihara, Nara 634
2Laboratory of Radiochemistry, Gifu Pharmaceutical University 6-1, Mitahora-higashi 5-chome, Gifu 502, Japan |
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Abstract: | The carcinogenic activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine(BHP) was investigated in male Wistar rats administered bis(2-hydroxypropyl)amine(BHPA) mixed in powder diet at a concentration of 1%, and sodiumnitrite (SN) dissolved in distilled water at concentrationsof 0.15 and 0.3%, for 94 weeks. Urinary excretion of BHP wasdetected in rats given 1% BHPA and 0.3% SN but not in the groupsreceiving either of these precursors alone. Nasal cavity, lung,esophagus, liver and urinary bladder tumors were found in animalstreated with combinations of 1% BHPA and 0.15 or 0.3% SN, suggestingthat the target organs of the endogenously synthesized BHP aresimilar to those affected when the carcinogen is administeredexogenously. The incidences of nasal cavity and lung tumorsreached 74 and 58% in rats given 1% BHPA and 0.3% SN, respectively.Tumors at sites other than target organs were only found atlevels similar to those previously reported for spontaneoustumors in male Wistars. The present results clearly indicatedthe tumor inducibility of a nhrosatable amine, BHA, throughan endogenous nitrosation by feeding to rats in conjunctionwith nitrite, and provide further suggestive evidence that endogenousnitrosations of environmental nitrosatable amines can be a potentialrisk factor in human cancer development. |
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