PMID- 32224358
OWN - NLM
STAT- MEDLINE
DCOM- 20200617
LR  - 20200617
IS  - 1879-1298 (Electronic)
IS  - 0045-6535 (Linking)
VI  - 252
DP  - 2020 Aug
TI  - Characterization of N-(2,6-dimethylphenyl)hydroxylamine adducts of 
      2'-deoxyguanosine under weakly basic conditions.
PG  - 126530
LID - S0045-6535(20)30723-2 [pii]
LID - 10.1016/j.chemosphere.2020.126530 [doi]
AB  - Aromatic amines are a class of chemical carcinogens that are activated by 
      cytochrome P450 enzymes to form arylhydroxylamines that are conjugated to form 
      N-acetoxyarylamines or N-sulfonyloxyarylamines. These conjugates undergo N-O bond 
      cleavage to become reactive nitrenium ions that may form DNA adducts. Numerous 
      studies in the past using N-acetoxyarylamines to investigate DNA adduct formation 
      were conducted, however, less is known in regard to DNA adduct formation directly 
      from arylhydroxylamines - especially under conditions that mimic the 
      physiological conditions of cells such as weakly basic conditions. In this study, 
      2'-deoxyguanosine (dG) was exposed to N-(2,6-dimethylphenyl)hydroxylamine 
      (2,6-DMPHA) and N-phenylhydroxylamine (PHA) at pH 7.4 without enzymes and 
      analyzed by liquid chromatography high resolution mass spectrometry (LC-HRMS). 
      2,6-DMPHA exposure resulted in the production of relatively low amounts of 
      adducts however the identities of at least six different adducts that were formed 
      through reactions with carbon, nitrogen and oxygen of 2'-deoxyguanosine were 
      proposed based upon different analytical approaches including HRMS CID 
      fragmentation and NMR analyses. Contrastively, PHA exposure under identical 
      conditions resulted in one adduct at the C8 position. It was concluded from these 
      results and results of theoretical calculations that nitrenium ions produced from 
      2,6-DMPHA were relatively more stable resulting in longer nitrenium ion lifetimes 
      which ultimately led to greater potential for 2,6-DMPHA nitrenium ions to react 
      with multiple sites on dG.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Matsui, Takuya
AU  - Matsui T
AD  - Department of Life and Environmental System Science, Graduate School of 
      Nanobiosciences, Yokohama City University, 22-2 Seto, Kanazawa, Kanagawa, 
      Yokohama, 236-0027, Japan; Toxicology Research Laboratories, Central 
      Pharmaceutical Research Institute Japan Tobacco Inc., 1-13-2 Fukuura, 
      Kanazawa-ku, Yokohama-city, Kanagawa, 236-0004, Japan.
FAU - Yamada, Naohito
AU  - Yamada N
AD  - Toxicology Research Laboratories, Central Pharmaceutical Research Institute Japan 
      Tobacco Inc., 1-13-2 Fukuura, Kanazawa-ku, Yokohama-city, Kanagawa, 236-0004, 
      Japan.
FAU - Kuno, Hideyuki
AU  - Kuno H
AD  - Toxicology Research Laboratories, Central Pharmaceutical Research Institute Japan 
      Tobacco Inc., 1-13-2 Fukuura, Kanazawa-ku, Yokohama-city, Kanagawa, 236-0004, 
      Japan.
FAU - Kanaly, Robert A
AU  - Kanaly RA
AD  - Department of Life and Environmental System Science, Graduate School of 
      Nanobiosciences, Yokohama City University, 22-2 Seto, Kanazawa, Kanagawa, 
      Yokohama, 236-0027, Japan. Electronic address: kanaly@yokohama-cu.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20200320
PL  - England
TA  - Chemosphere
JT  - Chemosphere
JID - 0320657
RN  - 0 (Carcinogens)
RN  - 0 (DNA Adducts)
RN  - 2FP81O2L9Z (Hydroxylamine)
RN  - G9481N71RO (Deoxyguanosine)
SB  - IM
MH  - Carcinogens/analysis
MH  - Chromatography, Liquid
MH  - DNA Adducts
MH  - DNA Damage
MH  - Deoxyguanosine/*metabolism
MH  - Hydroxylamine/metabolism
MH  - Magnetic Resonance Spectroscopy
MH  - Mass Spectrometry
OTO - NOTNLM
OT  - 2,6-dimethylaniline
OT  - 2'-deoxyguanosine
OT  - Aromatic amines
OT  - DNA adducts
OT  - LC-HRMS
OT  - N-(2,6-dimethylphenyl)hydroxylamine
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/04/01 06:00
MHDA- 2020/06/18 06:00
CRDT- 2020/04/01 06:00
PHST- 2019/11/26 00:00 [received]
PHST- 2020/03/14 00:00 [revised]
PHST- 2020/03/16 00:00 [accepted]
PHST- 2020/04/01 06:00 [pubmed]
PHST- 2020/06/18 06:00 [medline]
PHST- 2020/04/01 06:00 [entrez]
AID - S0045-6535(20)30723-2 [pii]
AID - 10.1016/j.chemosphere.2020.126530 [doi]
PST - ppublish
SO  - Chemosphere. 2020 Aug;252:126530. doi: 10.1016/j.chemosphere.2020.126530. Epub 
      2020 Mar 20.