Uptake and efflux of polycyclic aromatic hydrocarbons by Tetrahymena pyriformis: evidence for a resistance mechanism.
The action of benzo(a)pyrene (BP), 3-methylcholanthrene (3MC), benzanthracene (BA), and 7,12-dimethylbenzanthracene (DMBA), four polycyclic aromatic hydrocarbons (PAHs), was studied on the unicellular protozoan Tetrahymena pyriformis. This ciliate was exposed to the PAHs at 1, 15, and 37 microM for up to 6 h. BP and BA caused a slight inhibition of cell growth, whereas 3MC and DMBA showed no detectable effect. Cell viability remained unaffected by the PAHs at all concentrations and exposure times tested. Cellular accumulation of PAHs was studied using flow cytometry. The results show immediate accumulation followed by rapid elimination of the compounds. BP uptake was also studied in the presence of verapamil and cyclosporin, compounds known as inhibitors of the multidrug resistance (MDR) pump. In the presence of verapamil, BP was accumulated in larger amounts in cells. With cyclosporin, the accumulation of the PAH was several times higher than under control conditions. The results of GC/MS analysis show that PAH elimination was not linked to biotransformation. These results suggest that the resistance of Tetrahymena against PAH cytotoxicity may be attributed to the rapid efflux of these agents from the cells via an efflux pump probably of the MDR type.
Bamdad
M
M
Département de Chimie, Université du Québec à Montréal.
Reader
S
S
Grolière
C A
CA
Bohatier
J
J
Denizeau
F
F
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism* / Q000493:pharmacokinetics; D001580:Benzopyrenes / Q000378:metabolism* / Q000493:pharmacokinetics; D002273:Carcinogens / Q000378:metabolism* / Q000493:pharmacokinetics; D002455:Cell Division; D016572:Cyclosporine / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D008748:Methylcholanthrene / Q000378:metabolism* / Q000493:pharmacokinetics; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism / Q000493:pharmacokinetics; D013769:Tetrahymena pyriformis / Q000187:drug effects / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D002273:Carcinogens; D011084:Polycyclic Aromatic Hydrocarbons; D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D016572:Cyclosporine; C030935:benz(a)anthracene; D014700:Verapamil