TY - JOUR
T1 - DNA Adductome Analysis Identifies N-Nitrosopiperidine Involved in the Etiology of Esophageal Cancer in Cixian, China
AU - Totsuka, Yukari
AU - Lin, Yingsong
AU - He, Yutong
AU - Ishino, Kousuke
AU - Sato, Haruna
AU - Kato, Mamoru
AU - Nagai, Momoko
AU - Elzawahry, Asmaa
AU - Totoki, Yasushi
AU - Nakamura, Hiromi
AU - Hosoda, Fumie
AU - Shibata, Tatsuhiro
AU - Matsuda, Tomonari
AU - Matsushima, Yoshitaka
AU - Song, Guohui
AU - Meng, Fanshu
AU - Li, Dongfang
AU - Liu, Junfeng
AU - Qiao, Youlin
AU - Wei, Wenqiang
AU - Inoue, Manami
AU - Kikuchi, Shogo
AU - Nakagama, Hitoshi
AU - Shan, Baoen
N1 - Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/8/19
Y1 - 2019/8/19
N2 - Esophageal cancer is prevalent in Cixian, China, but the etiology of this disease remains largely unknown. Therefore, we explored this by conducting a DNA adductome analysis. Both tumorous and nontumorous tissues were collected from patients who underwent surgical procedures at Cixian Cancer Hospital and the Fourth Hospital of Hebei Medical University, which is in a low-incidence area. N2-(3,4,5,6-Tetrahydro-2H-pyran-2-yl)deoxyguanosine (THP-dG) was the major adduct detected in samples from esophageal cancer patients in Cixian. The precursor of THP-dG, N-nitrosopiperidine (NPIP), exhibited a strong mutagenic activity under metabolic activation in the Ames test and a significant dose-dependent increase in mutation frequency during an in vivo mutagenicity test with guanine phosphoribosyltransferase (gpt) delta rats. The NPIP-induced mutation was dominated by A:T to C:G transversions, followed by G:C to A:T and A:T to G:C transitions, in the liver and esophagus of animal samples. A similar mutational pattern was observed in the mutational signature of esophageal cancer patients that demonstrated weak correlation with THP-dG levels. These findings suggested that NPIP exposure is partly involved in the development of esophageal cancer in Cixian residents.
AB - Esophageal cancer is prevalent in Cixian, China, but the etiology of this disease remains largely unknown. Therefore, we explored this by conducting a DNA adductome analysis. Both tumorous and nontumorous tissues were collected from patients who underwent surgical procedures at Cixian Cancer Hospital and the Fourth Hospital of Hebei Medical University, which is in a low-incidence area. N2-(3,4,5,6-Tetrahydro-2H-pyran-2-yl)deoxyguanosine (THP-dG) was the major adduct detected in samples from esophageal cancer patients in Cixian. The precursor of THP-dG, N-nitrosopiperidine (NPIP), exhibited a strong mutagenic activity under metabolic activation in the Ames test and a significant dose-dependent increase in mutation frequency during an in vivo mutagenicity test with guanine phosphoribosyltransferase (gpt) delta rats. The NPIP-induced mutation was dominated by A:T to C:G transversions, followed by G:C to A:T and A:T to G:C transitions, in the liver and esophagus of animal samples. A similar mutational pattern was observed in the mutational signature of esophageal cancer patients that demonstrated weak correlation with THP-dG levels. These findings suggested that NPIP exposure is partly involved in the development of esophageal cancer in Cixian residents.
UR - http://www.scopus.com/inward/record.url?scp=85071703197&partnerID=8YFLogxK
U2 - 10.1021/acs.chemrestox.9b00017
DO - 10.1021/acs.chemrestox.9b00017
M3 - Article
C2 - 31286759
AN - SCOPUS:85071703197
SN - 0893-228X
VL - 32
SP - 1515
EP - 1527
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 8
ER -
