Effects of a diphenyl-ether herbicide, oxyfluorfen, on human BFU-E/CFU-E development and haemoglobin synthesis

Abstract

<jats:p> 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. </jats:p><jats:p> 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-Ery throid) were exposed to oxyfluorfen, a diphenyl-ether herbicide in the presence of erythropoietin, and the haematoxicity evaluated in vitro by scoring the develop ment 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 differentia tion showed a cytotoxic effect of oxyfluorfen only at very high concentrations. In contrast, haemoglobin synthesis can be inhibited by concentration of oxyfluorfen (10<jats:sup>-4</jats:sup> M) that have no adverse effect on cellular proliferation. </jats:p>

The use of cellular diagnostics for identifying sub-lethal stress in reef corals

“…Protoporphyrinogen oxidase IX levels were not affected, which suggests that ferrochelatase was a target of inhibition. Though PPO activity would have to be determined to confirm this possibility, that PPO levels were not depressed suggests that many of the diphenyl ether species could be excluded as potential suspects (Rio et al 1997).…”

Mitotic Index and Cell Proliferation Kinetics as Additional Variables for Assessment of Genotoxic Effect of The Herbicide Modown

“…oxyfluorfen, showed a cytotoxic effect in human erythroid progenitor cells only at very high concentrations (10 -4 M), but no adverse effect on cellular proliferation was seen (Rio et al 1997).…”

“…are extremely potent inhibitors of protoporphyrinogen oxidase, a membrane-bound enzyme involved in the heme and chlorophyll biosynthesis pathways (Camadro et al 1995). The later was studied for the induction of haematological diseases in human erythroid progenitor cells but a cytotoxic effect had been seen only at very high concentrations (Rio et al 1997).…”

Stem cells in myelotoxicity

“…In environmental toxicology, myelotoxicity of pesticides, natural toxins and chemicals has been demonstrated with hematopoietic clonogenic assays (Rio et al, 1997c;Van Den Heuvel et al, 2001;Malerba et al, 2002;Diodovich et al, 2003Diodovich et al, , 2004Diodovich et al, , 2005a.…”