O-6-alkylguanines, dietary N-nitroso compounds, and their precursors in gastric cancer

Several N-nitroso compounds, present in foods and beverages or formed in th e stomach from their precursors, act as alkylating agents. By using a highl y reliable technique (high-resolution gas chromatography-mass spectrometry with negative-ion chemical ionization and selected ion recording), we measu red a series of specific W-alkylguanines in snap-frozen paired stomach tiss ue samples (tumor and noninvolved mucosa) obtained at surgery from 24 gastr ic cancer patients identified in Florence, Italy. Samples of noninvolved mu cosa had higher levels of total O-6-alkylguanines and more frequently detec table levels (54%) than tumor samples (29.2%). O-6-propylguanine and O-6-me thylguanine were the single adducts most frequently detected in noninvolved mucosa and tumor tissue, respectively. Tumor samples showed higher levels of total O-6-alkylguanines in female patients (p = 0.03) and among those wi th a diffuse histological type (p = 0.06) or seronegative for Helicobacter pylori CagA antibodies (p = 0.06). Mean dietary nitrate intake was signific antly higher inpatients with detectable levels of adducts in tumor samples (p = 0.03). Estimated intakes of dimethylamine and N-nitrosodimethylamine c orrelated with total levels of O-6-alkylguanines in noninvolved gastric muc osa. These findings, although based on a small series of cases, support a r ole for N-nitroso compounds from dietary sources in the etiology of gastric cancer.