Human exposure to endogenous N-nitroso compounds: quantitative estimates in subjects at high risk for cancer of the oral cavity, oesophagus, stomach and urinary bladder.

A sensitive procedure to quantitate human exposure to endogenous N-nitroso compounds (NOC) has been developed. It is based on the excretion of N-nitrosoproline (NPRO) and other N-nitrosamino acids in the urine, which are measured as an index of endogenous nitrosation, following ingestion of precursors. The NPRO test has been applied to human subjects in clinical and epidemiological studies, and the kinetics and dietary modifiers of endogenous nitrosation have been investigated. Results obtained after application of the NPRO test to subjects at high risk for cancers of the stomach, oesophagus, oral cavity and urinary bladder are summarized. In most instances, higher exposures to endogenous NOC were found in high-risk subjects, but individual exposure was greatly affected by dietary modifiers or disease state. Vitamin C efficiently lowered the body burden of intragastrically formed NOC. The results point to an aetiological role of NOC in these human cancers and provide an interpretation of epidemiological findings that have shown protective effects of fruits and vegetables against several malignancies.