Effects of a diphenyl-ether herbicide, oxyfluorfen, on human BFU-E/CFU-E development and haemoglobin synthesis.
The diphenyl-ether herbicides exert their phytotoxic activity by preventing chlorophyll formation in plants as a result of inhibition of protoporphyrinogen oxidase. This enzyme is the last step of the common pathway for chlorophyll and haem biosynthesis. The aim of this work is to determine whether herbicide inhibitors of plant protoporphyrinogen oxidase could act on the human protoporphyrinogen oxidase involved in haemoglobin synthesis and cause heamatologic diseases. Human erythroblastic progenitors (BFU-E/CFU-E: Burst Forming Unit-Erythroid and Colony Forming Unit-Erythroid) were exposed to oxyfluorfen, a diphenyl-ether herbicide in the presence of erythropoietin, and the haematoxicity evaluated in vitro by scoring the development of BFU-E/CFU-E colonies after 7 and 14 days of culture. The toxic effect on differentiation has been evaluated using four criteria: morphology, total protein, total porphyrin, and haemoglobin content. The study of BFU-E/CFU-E proliferation and differentiation showed a cytotoxic effect of oxyfluorfen only at very high concentrations. In contrast, haemoglobin synthesis can be inhibited by concentration of oxyfluorfen (10(-4) M) that have no adverse effect on cellular proliferation.
Rio
B
B
Laboratoire de Microbiologie et Sécurité Alimentaire, Ecole Supérieure de Microbiologie et Sécurité Alimentaire de Brest, ISAMOR, Technopôle Brest-Iroise, Plouzané, France.
Parent-Massin
D
D
Lautraite
S
S
Hoellinger
H
H
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000502:physiology; D004920:Erythropoiesis / Q000187:drug effects*; D005312:Fetal Blood; D055768:Halogenated Diphenyl Ethers; D006454:Hemoglobins / Q000096:biosynthesis*; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D010647:Phenyl Ethers / Q000633:toxicity*; D011166:Porphyrins / Q000096:biosynthesis
D055768:Halogenated Diphenyl Ethers; D006454:Hemoglobins; D006540:Herbicides; D010647:Phenyl Ethers; D011166:Porphyrins; C016027:oxyfluorofen