Carcinogenic activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine in rats administered bis(2-hydroxypropyl)amine and sodium nitrite

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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 sodium nitrite (SN) dissolved in distilled water at concentrations of 0.15 and 0.3%, for 94 weeks. Urinary excretion of BHP was detected in rats given 1% BHPA and 0.3% SN but not in the groups receiving either of these precursors alone. Nasal cavity, lung, esophagus, liver and urinary bladder tumors were found in animals treated with combinations of 1% BHPA and 0.15 or 0.3% SN, suggesting that the target organs of the endogenously synthesized BHP are similar to those affected when the carcinogen is administered exogenously. The incidences of nasal cavity and lung tumors reached 74 and 58% in rats given 1% BHPA and 0.3% SN, respectively. Tumors at sites other than target organs were only found at levels similar to those previously reported for spontaneous tumors in male Wistars. The present results clearly indicated the tumor inducibility of a nhrosatable amine, BHA, through an endogenous nitrosation by feeding to rats in conjunction with nitrite, and provide further suggestive evidence that endogenous nitrosations of environmental nitrosatable amines can be a potential risk factor in human cancer development.