日本質量分析学会 第67回質量分析総合討論会

Abstract

Poster Presentations

Day 1, May 15(Wed.)  Room P (Multi-purpose Hall)

Application of DNA Adductomics Approach for Non-Targeted Screening Formaldehyde-Derived DNA Adducts by LC-QqQ-MS/MS with Constant Neutral Loss Scanning

(CSMU)
oJia-Wei Jian, Yuan-Jhe Chang, Pei-Shan Li, Chiung-Wen Hu, Mu-Rong Chao

Formaldehyde is known as a human carcinogen, and can induce the formation of DNA adducts, which is a key event for initiating carcinogenesis. Comprehensive measurement of DNA adducts induced by formaldehyde could help to elucidate the mechanism of carcinogenic action of formaldehyde. Recently, a novel methodology of DNA measurement was proposed, namely “DNA adductomics", which enables a comprehensive and simultaneous screening for known and unknown DNA adducts using mass spectrometry. Lately, we proposed a novel integrated approach to DNA adductomics using LC-QqQ-MS/MS in constant neutral loss (CNL) scan mode. In this study, we applied this method to profile/characterize the DNA adducts formation induced by formaldehyde. Calf thymus DNA was incubated with formaldehyde solution, and the DNA was then extracted, hydrolyzed and analyzed by LC-QqQ-MS/MS. Our adductome map revealed that a number of modified 2'-deoxyribonucleosides were newly formed in the treated DNA samples. These DNA adducts were identified by their precursor ion, and by the comparison of the product ion fragmentation profile with previously identified adducts reported in the literature. With this method, we successfully detected 8 known DNA adducts (including the major adduct N6-hydroxymethyl-2'-deoxyadenosine) and 5 unknown adducts induced by formaldehyde.