PMID- 23223497
OWN - NLM
STAT- MEDLINE
DCOM- 20130712
LR  - 20211021
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Print)
IS  - 0090-9556 (Linking)
VI  - 41
IP  - 2
DP  - 2013 Feb
TI  - Alteration of the expression of pesticide-metabolizing enzymes in pregnant mice: 
      potential role in the increased vulnerability of the developing brain.
PG  - 326-31
LID - 10.1124/dmd.112.049395 [doi]
AB  - Studies on therapeutic drug disposition in humans have shown significant 
      alterations as the result of pregnancy. However, it is not known whether 
      pesticide metabolic capacity changes throughout pregnancy, which could affect 
      exposure of the developing brain. We sought to determine the effect of pregnancy 
      on the expression of hepatic enzymes involved in the metabolism of pesticides. 
      Livers were collected from virgin and pregnant C57BL/6 mice at gestational days 
      (GD)7, GD11, GD14, GD17, and postpartum days (PD)1, PD15, and PD30. Relative mRNA 
      expression of several enzymes involved in the metabolism of pesticides, including 
      hepatic cytochromes (Cyp) P450s, carboxylesterases (Ces), and paraoxonase 1 
      (Pon1), were assessed in mice during gestation and the postpartum period. 
      Compared with virgin mice, alterations in the expression occurred at multiple 
      time points, with the largest changes observed on GD14. At this time point, the 
      expression of most of the Cyps involved in pesticide metabolism in the liver 
      (Cyp1a2, Cyp2d22, Cyp2c37, Cyp2c50, Cyp2c54, and Cyp3a11) were downregulated by 
      30% or more. Expression of various Ces isoforms and Pon1 were also decreased 
      along with Pon1 activity. These data demonstrate significant alterations in the 
      expression of key enzymes that detoxify pesticides during pregnancy, which could 
      alter exposure of developing animals to these chemicals.
FAU - Fortin, Marie C
AU  - Fortin MC
AD  - Environmental and Occupational Health Sciences Institute, Piscataway, NJ 08854, 
      USA.
FAU - Aleksunes, Lauren M
AU  - Aleksunes LM
FAU - Richardson, Jason R
AU  - Richardson JR
LA  - eng
GR  - T32 ES007148/ES/NIEHS NIH HHS/United States
GR  - P30 ES005022/ES/NIEHS NIH HHS/United States
GR  - ES020522/ES/NIEHS NIH HHS/United States
GR  - K99 DK080774/DK/NIDDK NIH HHS/United States
GR  - R01 ES015991/ES/NIEHS NIH HHS/United States
GR  - R01 ES020522/ES/NIEHS NIH HHS/United States
GR  - R00 DK080774/DK/NIDDK NIH HHS/United States
GR  - ES015991/ES/NIEHS NIH HHS/United States
GR  - ES007148/ES/NIEHS NIH HHS/United States
GR  - ES005022/ES/NIEHS NIH HHS/United States
GR  - DK080774/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121204
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Isoenzymes)
RN  - 0 (Pesticides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Transcription Factors)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 3.1.1.1 (Carboxylesterase)
RN  - EC 3.1.8.1 (Aryldialkylphosphatase)
RN  - EC 3.1.8.1 (PON1 protein, mouse)
SB  - IM
CIN - Drug Metab Dispos. 2013 Feb;41(2):256-62. PMID: 23328895
MH  - Animals
MH  - Aryldialkylphosphatase/genetics/*metabolism
MH  - Biotransformation
MH  - Brain/drug effects/embryology
MH  - Carboxylesterase/genetics/*metabolism
MH  - Cytochrome P-450 Enzyme System/genetics/*metabolism
MH  - Female
MH  - Gene Expression Regulation, Enzymologic
MH  - Gestational Age
MH  - Isoenzymes
MH  - Liver/*enzymology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurotoxicity Syndromes/embryology/etiology
MH  - Pesticides/*metabolism/toxicity
MH  - Pregnancy
MH  - RNA, Messenger/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/genetics/metabolism
MH  - Substrate Specificity
MH  - Transcription Factors/genetics/metabolism
PMC - PMC3558862
EDAT- 2012/12/12 06:00
MHDA- 2013/07/16 06:00
PMCR- 2014/02/01
CRDT- 2012/12/11 06:00
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/07/16 06:00 [medline]
PHST- 2014/02/01 00:00 [pmc-release]
AID - dmd.112.049395 [pii]
AID - DMD_049395 [pii]
AID - 10.1124/dmd.112.049395 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2013 Feb;41(2):326-31. doi: 10.1124/dmd.112.049395. Epub 2012 
      Dec 4.