Experimental studies: N-nitroso compounds

Introduction

The esophagus is an organ which might not be expected to be especially sensitive to chemical carcinogens. After ingestion, food and drink remain for a short period in the mouth, for a much longer time in the stomach, but pass rapidly through the lumen of the esophagus. Exposure of the oral and gastric mucosa is of very much longer duration than that of the esophageal epithelium, so that direct-acting chemicals, i.e. those which do not require metabolic activation to be effective carcinogens, are more likely to cause oral or gastric cancer. Chemicals which remain inert until activated by metabolism can be absorbed into the circulation and reach the esophagus by this route. However, the chemicals which do require metabolic activation before they become effective are more likely to be carcinogenic for the more metabolically active organs, i.e. liver and kidney, than for organs with lower metabolic activity, and lower cytochrome P450 levels, such as muscle, nerve and esophagus.

In general, this concept appears to be justified, as of all the huge number of chemicals which have been tested for carcinogenicity, very few are carcinogenic for the esophagus. The outstanding exception is a large group of compounds which are very potent esophageal carcinogens: the Nnitrosamines. The outstanding exception is a large group of compounds which are very potent esophageal carcinogens: the N-nitrosamines.