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ABC and P-450

miller rellim at MAILHOST.TCS.TULANE.EDU
Thu Feb 4 18:24:18 EST 1999


Andrey.L.Sukhodub at univer.kharkov.ua, wrote:

>Can anybody help me with the understanding of ATP-binding cassette
>proteins >(ABC)multidrug-resistant protein and cytochrome P-450
>physiological interactions? Especially in >mammals. I'll highly appreciate
>any advice.


The ABC (for ATP-Binding Cassette) transporters are plasma membrane pumps
that export a number of drugs, xenobiotics, hormones, etc. from cells in an
ATP-dependent manner. P450s are in the smooth endoplasmic reticulum, and
they metabolize a number of the same compounds. Sometimes the ABC
transporters bind and export  compounds before they are metabolized, and
sometimes P450 action is required prior to interaction with the ABC
transporter--it depends on the compound. A good example is estradiol
glucuronide, which is a physiological substrate for the human ABC
transporter called MDR1 (for Multiple Drug Resistance). This transporter
was discovered for its amplification/overexpression in tumors and its role
in resistance to anti-tumor drugs. Excess MDR1 helps drug-resistant tumor
cells pump out cytotoxic compounds. Some of these same compounds require
P450 metabolism to achieve their ultimate toxic form. Cells that can pump
out the drug before it gets metabolized or reacts with critical targets
will survive. There is a large literature on this subject. Try searching
MDR1 and P450 at some of the sites listed in the FAQ for this newsgroup,
especially the National Cancer Institute (NCI) or Medline web sites.

Chuck


Dr. Charles A. Miller III,   rellim at mailhost.tcs.tulane.edu
Dept. Environmental Health Sciences, SL29
Tulane-Xavier Center for Bioenvironmental Research and
Tulane Univ. School of Public Health and Tropical Medicine
1430 Tulane Ave.
New Orleans, LA 70112
(504)585-6942, fax (504)584-1726
Bionet.toxicology newsgroup: http://www.bio.net/hypermail/TOXICOLOGY





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