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Suppressive effect of tobacco smoke extracts on oral P-glycoprotein function and its impact in smoke-induced insult to oral epidermal cells.

Abstract：

:P-glycoprotein (Pgp) participates in the export of numerous toxins, drugs, and physiological compounds. To examine the involvement of Pgp in smoke-induced oral cell insult, the effects of extracts of the mainstream tobacco smoke (TS) on Pgp were studied in an oral epidermal carcinoma cell line, OECM-1. TS was first extracted with cyclohexane (CTS) and the residues were further extracted with isopropanol (ITS). For comparison, cells were exposed to CTS and ITS at the concentrations according to their relative extraction yield. ITS but not CTS decreased the efflux of a Pgp substrate, rhodamine (Rh) 123, in a concentration- and time-dependent manner. The efflux was also decreased by co-exposure to CTS and ITS. However, immunoblot analysis revealed that the protein level of Pgp was not affected by ITS. Naphthalene, mainly detected in the ITS, decreased Rh 123 efflux. However, the efflux activity was not affected by benzo(a)pyrene and nicotine, which were present in the CTS and both extracts, respectively. Co-exposure to CTS in combination with ITS, naphthalene, or verapamil enhanced cell insult compared to single exposure. These results demonstrated that smoke and its constituent, naphthalene, diminished Pgp-mediated efflux. The reduction in Pgp function could be a stimulatory factor of TS-induced oral cell insult.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Pan WC,Chen RM,Shen YC,Chen CC,Ueng YF

doi

10.1016/j.toxlet.2008.12.007

subject

Has Abstract

pub_date

2009-03-10 00:00:00

pages

116-23

issue

2

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(08)01383-0

journal_volume

185

pub_type

杂志文章

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