Previous studies in Linxian, an area of China with a high incidence of esophageal carcinoma, showed that fungal infections are common in the esophageal epithelium of patients with either premalignant changes or early esophageal carcinoma. Fungi of the genus Candida were the most frequent invaders. In these areas nitrate and nitrite are often present in high, concentrations in drinking. water and staple grains. The present studies have-established the ability of Candida albicana to augment the nitrosative formation of the esophagus-specific carcinogen, benzylmethylnitrosamine (NBMA; N-nitroso-N-methylbenzylamine).Stationary C. albicans cultures~with pH held at, 6.8 were incubated with the precursors of NBMA, benzylmethylamine (BMA, N-methylbenzylamine) and Na02. There was a significant increase in the amount of NBMA formed in these cultures, compared to precursors-only controls. The amount of NBMA synthesized depended on fungal cell number. Exponentially growing cultures were also able to cause NBMA formation. The identity of the NBMA was confirmed by high-performance liquid chromatographic coelution with authentic NBMA in three solvent systems and by mass spectroscopy. Boiled cells and conditioned medium in which cells had been.incubated were not effective in enhancing nitrosation, Cultured Candida released acidic metab-. olites that reduced the pH of the medium when only a low concentration of buffer was present. Spontaneous nitrosation of BMA was enhanced under these acidic conditions..Thus, C. albicans infecting the esophageal epithelium could cause local formation of NBMA by both cell-mediated catalysis and extracellular decrease in pH.Esophageal carcinoma is the second most common cancer in China, causing 157,000 deaths every year. In Linxian, a county in Northern Honan province, the incidence of esophageal cancer is 178 per 100,000 people per annum, with a death rate of 132 per 100,000 (1). Pathological investigations in Linxian showed that fungal infections were often associated with hyperplasia or dysplasia of the esophageal' epithelium in patients with premalignant changes or early carcinoma (2). More than half of the fungi found in the epithelium were Candida species; Candida albicans was isolated from the hyperplastic epithelium of a patient with esophageal carcinoma in situ: (2). Anti-candida antibody titers were also high in the infected patients (3; unpublished data). An association between fungal infections and esophageal carcinoma was suggested.Are Candida infections of the esophagus causally linked to development of cancer in this tissue? Stimulation of hyperplasia, release of tumor-promoting agents,. and formation of carcinogens. are, possible mechanisms by which fungi could' contribute to the appearance of tumors. Fungi and other microorganisms may enhance formation of nitrosamines from naturally occurring precursors (4-6), and certain nitrosamines are specific inducers of esophageal tumors in rodents (7,8). It is possible that Candida participates in the causation of esophageal cance...