Effects of human milk and formula on the transcriptional regulation of cytochrome P450 3A4 in HepG2 cells.
Published: 2004
Language: eng
Number of pages: 81
Description: Caffeine is eliminated nearly 3-fold faster in formula-fed infants. As cytochrome P450 3A4 (CYP3A4) is a major caffeine metabolizer and as its expression is primarily regulated by the human pregnane X receptor (hPXR), we postulate that formula induces CYP3A4 expression through hPXR activation. The human liver-derived cell line, HepG2, was tested for CYP3A4 mRNA expression after incubation with undigested human milk and formula. A reporter construct containing CYP3A4-PXR binding elements were transfected into HepG2 cells and examined for activation by milk. CYP3A4 mRNA was increased 2--3 fold and reporter activity was mildly induced after all milk treatments. hPXR expression plasmid co-transfection modestly augmented reporter activity only with bovine-based formula. These results suggest that CYP3A4 induction by formula does not account for differences in caffeine elimination between breastfed and formula-fed infants. Furthermore, PXR-mediated regulation most likely does not play a major role in the transcriptional induction of CYP3A4 by milk.
Notes: Adviser:  Shinya Ito.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 43-03, page: 0832.

MICR copy on microfiche (1 microfiche).