title: Inhibition of human MDR1 and BCRP transporter ATPase activity by organochlorine and pyrethroid insecticides.
abstract: Despite the growing evidence suggesting that pesticides contribute to chronic diseases, there is a limited understanding of how these chemicals are removed from cells and whether pesticides can alter the disposition of drugs. The present study examined the effects of two classes of insecticides (organochlorine and pyrethroid) on the ATPase activity of the human multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) efflux transporters. Using plasma membranes from cells overexpressing MDR1 and BCRP, it was demonstrated that the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) (o,p'-DDT and p,p'-DDT isomers) as well as its metabolite (p,p'-dichlorodiphenyldichloroethane), inhibit both MDR1 and BCRP ATPase activity. In addition, p,p'-dichlorodiphenyldichloroethylene, and two pyrethroid pesticides inhibited BCRP ATPase activity between 4 and 7 μM. Additional research is necessary to further characterize the functional inhibition of MDR1 and BCRP activity and determine whether pesticides alter the transporter-mediated disposition of other chemicals.
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Bircsak
authors.forename: Jason R
authors.initials: JR
authors.lastname: Richardson
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Aleksunes
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003634:DDT / Q000494:pharmacology*; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011722:Pyrethrins / Q000494:pharmacology*; D061987:Sf9 Cells; D018411:Spodoptera
chemical_list: C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D007306:Insecticides; D009363:Neoplasm Proteins; D011722:Pyrethrins; D003634:DDT