PMID- 27125825
OWN - NLM
STAT- MEDLINE
DCOM- 20170713
LR  - 20170817
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 91
IP  - 2
DP  - 2017 Feb
TI  - The long persistence of pyrrolizidine alkaloid-derived DNA adducts in vivo: 
      kinetic study following single and multiple exposures in male ICR mice.
PG  - 949-965
LID - 10.1007/s00204-016-1713-z [doi]
AB  - Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and the 
      most common poisonous plants affecting livestock, wildlife, and humans. Our 
      previous studies demonstrated that PA-derived DNA adducts can potentially be a 
      common biological biomarker of PA-induced liver tumor formation. In order to 
      validate the use of these PA-derived DNA adducts as a biomarker, it is necessary 
      to understand the basic kinetics of the PA-derived DNA adducts formed in vivo. In 
      this study, we studied the dose-dependent response and kinetics of PA-derived DNA 
      adduct formation and removal in male ICR mice orally administered with a single 
      dose (40 mg/kg) or multiple doses (10 mg/kg/day) of retrorsine, a representative 
      carcinogenic PA. In the single-dose exposure, the PA-derived DNA adducts 
      exhibited dose-dependent linearity and persisted for up to 4 weeks. The removal 
      of the adducts following a single-dose exposure to retrorsine was biphasic with 
      half-lives of 9 h (t (1/2alpha)) and 301 h (~12.5 days, t (1/2beta)). In the 8-week 
      multiple exposure study, a marked accumulation of PA-derived DNA adducts without 
      attaining a steady state was observed. The removal of adducts after the multiple 
      exposure also demonstrated a biphasic pattern but with much extended half-lives 
      of 176 h (~7.33 days, t (1/2alpha)) and 1736 h (~72.3 days, t (1/2beta)). The lifetime 
      of PA-derived DNA adducts was more than 8 weeks following the multiple-dose 
      treatment. The significant persistence of PA-derived DNA adducts in vivo supports 
      their role in serving as a biomarker of PA exposure.
FAU - Zhu, Lin
AU  - Zhu L
AD  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of 
      Hong Kong, Shatin, Hong Kong SAR, China.
AD  - Joint Research Laboratory of Promoting Globalization of Traditional Chinese 
      Medicines Between The Chinese University of Hong Kong and Shanghai Institute of 
      Materia Medica, Chinese Academy of Sciences, Shanghai, China.
FAU - Xue, Junyi
AU  - Xue J
AD  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of 
      Hong Kong, Shatin, Hong Kong SAR, China.
AD  - Joint Research Laboratory of Promoting Globalization of Traditional Chinese 
      Medicines Between The Chinese University of Hong Kong and Shanghai Institute of 
      Materia Medica, Chinese Academy of Sciences, Shanghai, China.
FAU - Xia, Qingsu
AU  - Xia Q
AD  - National Center for Toxicological Research, Jefferson, AR, 72079, USA.
FAU - Fu, Peter P
AU  - Fu PP
AD  - National Center for Toxicological Research, Jefferson, AR, 72079, USA. 
      peter.fu@fda.hhs.gov.
FAU - Lin, Ge
AU  - Lin G
AD  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of 
      Hong Kong, Shatin, Hong Kong SAR, China. linge@cuhk.edu.hk.
AD  - Joint Research Laboratory of Promoting Globalization of Traditional Chinese 
      Medicines Between The Chinese University of Hong Kong and Shanghai Institute of 
      Materia Medica, Chinese Academy of Sciences, Shanghai, China. linge@cuhk.edu.hk.
LA  - eng
PT  - Journal Article
DEP - 20160428
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (DNA Adducts)
RN  - 0 (Pyrrolizidine Alkaloids)
RN  - XJ86XWL8IY (retrorsine)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - DNA Adducts/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Liver/drug effects/pathology
MH  - Male
MH  - Mice, Inbred ICR
MH  - Pyrrolizidine Alkaloids/administration & dosage/*toxicity
OTO - NOTNLM
OT  - Biomarker
OT  - DNA adducts
OT  - Kinetics
OT  - Pyrrolizidine alkaloid
EDAT- 2016/04/30 06:00
MHDA- 2017/07/14 06:00
CRDT- 2016/04/30 06:00
PHST- 2016/01/05 00:00 [received]
PHST- 2016/04/14 00:00 [accepted]
PHST- 2016/04/30 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/04/30 06:00 [entrez]
AID - 10.1007/s00204-016-1713-z [pii]
AID - 10.1007/s00204-016-1713-z [doi]
PST - ppublish
SO  - Arch Toxicol. 2017 Feb;91(2):949-965. doi: 10.1007/s00204-016-1713-z. Epub 2016 
      Apr 28.