ラットの生体内で生成されたN-nitrosobis(2-hydroxypropyl)amineの発癌性に関する研究

Abstract

Carcinogenic activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine (BHP) from bis(2-hydroxypropyl)amine (BHPA) and tris(2-hydroxypropyl)amine (THPA) in the presence of sodium nitrite (SN) was investigated in male Wistar rats. The following results were obtained. 1) The synthesis of BHP from BHPA and THPA in the presence of SN was demonstrated in vitro and in vivo in the preliminary experiment and also confirmed by the urinary excretion of BHP in rats treated with 1% BHPA and 2% THPA in diet together with 0.3% SN in drinking water. 2) Tumors in nasal cavity and lung were induced in rats treated with 1% BHPA in diet together with 0.3% SN in drinking water for 94 weeks, the incidences of which reached 74% and 58%, respectively. However, no tumors were found in the target organs of BHP in rats treated with 2% THPA in diet and 0.3% SN in drinking water for 102 weeks. 3) The initiation activity for liver by endogenously synthesized BHP was observed in rats treated with 1% BHPA in diet together with 0.15% and 0.3% SN in drinking water by the quantitative analysis of glutathione S-transferase placental form (GST-P)-positive foci but was not observed in rats treated with 2% THPA in diet together with 0.15% and 0.3% SN in drinking water. These results indicate that endogenously synthesized BHP has a carcinogenic activity similar to that of exogenously administered BHP, and that BHPA is more important as the precursor for endogenous BHP synthesis. Since the precursors of nitrosamines are widely distributed in the environment, endogenously synthesized nitrosamines may play an important role in the development of human cancer.