Geospatial Assessments of DNA Adducts in the Human Stomach: A Model of Field Cancerization

SIMPLE SUMMARY: The geospatial distribution of DNA adducts, the presumable origins of mutations causing human cancers in the stomach was described. In human stomach resections for gastric cancer, seven different DNA adducts, C5-methyl-2′-deoxycytidine, 2′-deoxyinosine, C5-hydroxymethyl-2′-deoxycytidine, N6-methyl-2′-deoxyadenosine, 1,N6-etheno-2′-deoxyadenosine, N6-hydroxymethyl-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine, were identified in various parts and zones of the human stomach, namely, the upper, middle and lower zones, anterior and posterior walls, and lesser and greater curvatures. This DNA adductomics approach will reveal the exposure and risk of individual gastric mucosa in humans. Basic information on multiple DNA adduct profiles in terms of the correlation with the preferred locations of gastric cancer in the stomach will provide the reality of “field cancerization” in human gastric carcinogenesis. ABSTRACT: Background: Field cancerization is a popular concept regarding where cancer cells arise in a plane, such as the opened-up gastrointestinal mucosa. The geospatial distribution of DNA adducts, some of which are believed to initiate mutation, may be a clue to understanding the landscape of the preferred occurrence of gastric cancer in the human stomach, such that the occurrence is much more frequent in the lesser curvature than in the greater curvature. Methods: Seven DNA adducts, C5-methyl-2′-deoxycytidine, 2′-deoxyinosine, C5-hydroxymethyl-2′-deoxycytidine, N6-methyl-2′-deoxyadenosine, 1,N6-etheno-2′-deoxyadenosine, N6-hydroxymethyl-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine, from different points and zones of the human stomach were semi quantitatively measured by liquid chromatography/tandem mass spectrometry. The differences in the quantity of these DNA adducts from the lesser and greater curvature, the upper, middle and lower third zones, the anterior and posterior wall of the stomach, and the mucosae distant from and near the tumor were compared to determine whether the location preference of cancer in the stomach could be explained by the distribution of these DNA adducts. Comparisons were conducted considering the tumor locations and operation methods. Conclusions: Regarding the DNA adducts investigated, significant differences in quantities and locations in the whole stomach were not noted; thus, these DNA adducts do not explain the preferential occurrence of cancer in particular locations of the human stomach.