Mass spectrometric profiling of DNA adducts in the human stomach associated with damage from environmental factors

Genes and environment

Yoshitaka Matsushima¹  Nobuhito Kurono²  Haruhiko Sugimura³  Yuji Iwashita³  Yuto Matsushita⁴  Takashi Yamashita⁵  Shunsuke Ohtsuka⁶  Ippei Ohnishi⁷  Hiroki Mori⁸  Shioto Suzuki⁹  Fumihiko Tanioka⁹  Hideto Ochiai^1,10  Atsuko Fukazawa^1,10  Shohachi Suzuki^1,10  Keigo Matsumoto^1,10  Keisuke Inaba^1,10 

[1] Department of Agricultural Chemistry, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, 156-8502, Tokyo, Japan;Department of Chemistry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Shizuoka, Japan;Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Shizuoka, Japan;Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Shizuoka, Japan;Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Shizuoka, Japan;Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Shizuoka, Japan;First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Shizuoka, Japan;Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Shizuoka, Japan;Hamamatsu Medical Center, 328 Tomitsuka-cho, Naka-ku, Hamamatsu, 432-8580, Shizuoka, Japan;Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Shizuoka, Japan;Pathology Division, Iwata City Hospital, 512-3 Ohkubo, Iwata, 438-8550, Shizuoka, Japan;Hamamatsu Medical Center, 328 Tomitsuka-cho, Naka-ku, Hamamatsu, 432-8580, Shizuoka, Japan;Pathology Division, Iwata City Hospital, 512-3 Ohkubo, Iwata, 438-8550, Shizuoka, Japan;Surgery Division, Iwata City Hospital, 512-3 Ohkubo, Iwata, 438-8550, Shizuoka, Japan;

关键词: DNA adduct;    DNA adductome;    DNA adductomics;    Mutagen;    Exposure;    Stomach;    Gastric cancer;    Liquid chromatography/tandem mass spectrometry;   

DOI  :  10.1186/s41021-021-00186-2

来源: Springer

【 摘 要 】

BackgroundA comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this “DNA adductome approach” in human tissues have been reported. Geospatial information on DNA adducts in human organs has been scarce.AimMass spectrometry of human gastric mucosal DNA was performed to identify DNA adducts associated with environmental factors.Materials and methodsFrom 59 subjects who had received gastrectomy for gastric cancer, 306 samples of nontumor tissues and 15 samples of tumors (14 cases) were taken for DNA adductome analysis. Gastric nontumor tissue from autopsies of 7 subjects without gastric cancer (urothelial cancer, hepatocellular carcinoma, lung cancer each; the other four cases were without any cancers) was also investigated. Briefly, DNA was extracted from each sample with antioxidants, digested into nucleosides, separated by liquid chromatography, and then electrospray-ionized. Specific DNA adducts were identified by mass/charge number and column retention time compared to standards. Information on lifestyle factors such as tobacco smoking and alcohol drinking was taken from the clinical records of each subject.ResultsSeven DNA adducts, including modified bases, 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 the human stomach and characterized. Intraindividual differences according to the multiple sites of these adducts were noted but were less substantial than interindividual differences. N6-hydroxymethyl-2′-deoxyadenosine was identified in the human stomach for the first time. The amount of C5-hydroxymethyl-2′-deoxycytidine was higher in the stomachs of subjects without gastric cancer than in the nontumor and tumor portions of the stomach in gastric cancer patients. Higher levels of 1,N6-etheno-2′-deoxyadenosine were detected in the subjects who reported both smoking and drinking than in those without these habits. These DNA adducts showed considerable correlations with each other.ConclusionsWe characterized 7 DNA adducts in the nontumor portion of the human stomach in both gastric cancer subjects and nongastric cancer subjects. A reduction in C5-hydroxymethyl-dC even in the nontumor mucosa of patients with gastric cancer was observed. Smoking and drinking habits significantly influenced the quantity of one of the lipid peroxidation-derived adducts, etheno-dA. A more expansive DNA adductome profile would provide a comprehensive understanding of the origin of human cancer in the future.

【 授权许可】

CC BY