Transnitrosation by nitrosamines in vivo.

The significance of in vivo transnitrosation in carcinogenesis by the nitrosamines formed was studied by feeding mixtures of morpholine and nitrosamines to rats for most of their lifespan. In some groups, a transnitrosation catalyst (sodium thiocyanate) was fed simultaneously. None of the four nitrosamines induced a significant number of liver tumours when fed singly, although nitrosophenylbenzylamine induced tumours of the spleen and upper gastrointestinal tract and nitroso-N-methylpiperazine induced tumours of the nasal cavity. Nitrosoproline taken with morpholine did not give rise to tumours, except when given in combination with sodium thiocyanate, which gave rise to an even higher frequency of hepatic tumours when given alone. Nitrosohydroxyproline with morpholine induced liver carcinomas in 3 of 20 rats and in 9 of 20 rats in the presence of sodium thiocyanate. Rats given nitrosophenylbenzylamine plus morpholine lived less than 2 years and 4 of them had liver tumours. Most rats treated with nitrosomethylpiperazine died within a year, because of the tumours induced; the combination with morpholine hydrochloride led to the formation of liver carcinomas in 2 of 20 rats and in 5 of 20 when thiocyanate was given.