title: Generation of resistance to the diphenyl ether herbicide acifluorfen by MEL cells.
abstract: The diphenyl ether herbicide acifluorfen has been shown to act by inhibition of the terminal enzyme of the protoporphyrin biosynthetic pathway, protoporphyrinogen oxidase (E.C. 1.3.3.4) (PPO), in plant and animal cells. In the present study we show that long term maintenance of murine erythroleukemia (MEL) cells in acifluorfen, which is normally toxic to these cells at 5 microM concentration, results in cells that grow at a near normal rate in 100 microM acifluorfen. Acifluorfen resistant cells do not have increased levels of PPO activity, nor does the PPO made by these cells have increased resistance to acifluorfenin, but these cells accumulate porphyrin and have elevated levels of heme. Data is presented that suggests the resistance of these MEL cells to acifluorfen may be attributable to induction of a cytochrome P450(s).
authors.affiliation: Department of Microbiology, University of Georgia, Athens 30602-2605, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Prasad
authors.forename: H A
authors.initials: HA
authors.lastname: Dailey
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004351:Drug Resistance; D004790:Enzyme Induction / Q000187:drug effects; D005420:Flavoproteins; D006418:Heme / Q000378:metabolism; D006540:Herbicides / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D024101:Mitochondrial Proteins; D009579:Nitrobenzoates / Q000494:pharmacology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011166:Porphyrins / Q000378:metabolism; D050768:Protoporphyrinogen Oxidase; D014407:Tumor Cells, Cultured
chemical_list: D005420:Flavoproteins; D006540:Herbicides; D024101:Mitochondrial Proteins; D009579:Nitrobenzoates; D011166:Porphyrins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493979:Ppox protein, mouse; D050768:Protoporphyrinogen Oxidase; C018425:acifluorfen