PMID- 15997229
OWN - NLM
STAT- MEDLINE
DCOM- 20051209
LR  - 20181201
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 146
IP  - 2
DP  - 2005 Sep
TI  - Induction of cytochrome P450 1A by cow milk-based formula: a comparative study 
      between human milk and formula.
PG  - 296-305
AB  - During the treatment of neonatal apnea, formula-fed infants, compared to 
      breastfed infants, show nearly three-fold increase in clearance of caffeine, a 
      substrate of cytochrome P450 1A (CYP1A) and in part CYP3A4. However, human milk 
      is known to contain higher concentrations of environmental pollutants than infant 
      formula, which are potent CYP1A inducers. To gain insight into the mechanism 
      underlying this apparent contradiction, we characterized CYP1A and CYP3A4 
      induction by human milk and cow milk-based infant formula. The mRNA and protein 
      expression of CYP1A1/1A2 were significantly induced by cow milk-based formula, 
      but not by human milk, in HepG2 cells. Luciferase reporter assay demonstrated 
      that cow milk-based formula but not human milk activated aryl hydrocarbon 
      receptor (AhR) significantly. The cotreatment of 3,4-dimethoxyflavone, an AhR 
      antagonist, abolished the formula-induced CYP1A expression. In addition, AhR 
      activation by dibenzo[a,h]anthracene, a potent AhR agonist, was significantly 
      suppressed by infant formula and even more by human milk. In contrast, CYP3A4 
      mRNA expression was only mildly induced by formula and human milk. Consistently, 
      neither formula nor human milk substantially activated pregnane X receptor (PXR). 
      Effects of whey and soy protein-based formulas on the AhR-CYP1A and the 
      PXR-CYP3A4 pathways were similar to those of cow milk-based formula. In 
      conclusion, infant formula, but not human milk, enhances in vitro CYP1A 
      expression via an AhR-mediated pathway, providing a potential mechanistic basis 
      for the increased caffeine elimination in formula-fed infants.
FAU - Xu, Haibo
AU  - Xu H
AD  - Division of Clinical Pharmacology & Toxicology, Hospital for Sick Children, 555 
      University Avenue, Toronto, Ontario, Canada M5G 1X8.
FAU - Rajesan, Ratheishan
AU  - Rajesan R
FAU - Harper, Patricia
AU  - Harper P
FAU - Kim, Richard B
AU  - Kim RB
FAU - Lonnerdal, Bo
AU  - Lonnerdal B
FAU - Yang, Mingdong
AU  - Yang M
FAU - Uematsu, Satoko
AU  - Uematsu S
FAU - Hutson, Janine
AU  - Hutson J
FAU - Watson-MacDonell, Jo
AU  - Watson-MacDonell J
FAU - Ito, Shinya
AU  - Ito S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Environmental Pollutants)
RN  - 0 (Isoenzymes)
RN  - 0 (Milk Proteins)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Pregnane X Receptor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Soybean Proteins)
RN  - 0 (Whey Proteins)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cattle
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Cytochrome P-450 Enzyme System/*biosynthesis
MH  - Electrophoretic Mobility Shift Assay
MH  - Environmental Pollutants/toxicity
MH  - Enzyme Induction/drug effects
MH  - Genes, Reporter/genetics
MH  - Humans
MH  - Infant
MH  - Infant Food/*adverse effects
MH  - Infant, Newborn
MH  - Isoenzymes/biosynthesis
MH  - Luciferases/genetics
MH  - Milk/*chemistry
MH  - Milk Proteins/pharmacology
MH  - Milk, Human/*chemistry
MH  - Polychlorinated Dibenzodioxins/toxicity
MH  - Pregnane X Receptor
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Receptors, Aryl Hydrocarbon/agonists/genetics
MH  - Receptors, Cytoplasmic and Nuclear/drug effects/genetics
MH  - Receptors, Steroid/drug effects/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Soybean Proteins/pharmacology
MH  - Whey Proteins
PMC - PMC1576269
EDAT- 2005/07/06 09:00
MHDA- 2005/12/13 09:00
PMCR- 2006/09/01
CRDT- 2005/07/06 09:00
PHST- 2005/07/06 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/07/06 09:00 [entrez]
PHST- 2006/09/01 00:00 [pmc-release]
AID - 0706319 [pii]
AID - 10.1038/sj.bjp.0706319 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2005 Sep;146(2):296-305. doi: 10.1038/sj.bjp.0706319.