Isofenphos induced metabolic changes in K562 myeloid blast cells.
The organophosphate pesticide, isofenphos, is associated with human myeloid leukemia. In this study we describe metabolic changes in K562 myeloid blast cells from exposure to varying concentrations of isofenphos using the stable [1,2-13C(2)]glucose isotope as the single tracer and biological mass spectrometry. Isofenphos (1, 10, 100 microg/ml/72 h) treated K562 cells showed increases of 10.7, 33.8 and 39.7% in lactate production as well as a 14.2% increase (1 microg/ml/72 h) in 13C incorporation into nucleic acid ribose from glucose. Concomitantly, we observed a decrease in glucose oxidation and the synthesis of glutamate, palmitate and stearate from glucose. Our results demonstrate that this organophosphate pesticide exerts a leukemogenic effect by the recruitment of glucose carbons for nucleic acid synthesis thus promoting proliferation simultaneous with poor differentiation. The imbalanced metabolic phenotype with a severe defect in glucose oxidation, lipid and amino acid synthesis concurrent with de novo synthesis of nucleic acids in response to isofenphos treatment conforms to the invasive proliferating phenotype observed in TGF-beta treated lung epithelial carcinoma cells.
Boros
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LG
Harbor-UCLA Research and Education Institute, UCLA School of Medicine, 1124 West Carson Street RB1, Torrance, CA 90502, USA.
Williams
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RD
D005227:Fatty Acids / Q000032:analysis; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D020014:K562 Cells / Q000187:drug effects* / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D013058:Mass Spectrometry; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D010427:Pentose Phosphate Pathway; D012313:RNA / Q000378:metabolism; D012266:Ribose / Q000378:metabolism
D005227:Fatty Acids; D007306:Insecticides; D009946:Organothiophosphorus Compounds; C035019:isofenphos; D019344:Lactic Acid; D018698:Glutamic Acid; D012313:RNA; D012266:Ribose; D005947:Glucose