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 blas t cells from exposure to varying concentrations of isofenphos using the sta ble [1,2-C-13(2)]glucose isotope as the single tracer and biological mass s pectrometry. Isofenphos (1, 10, 100 mug/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 mug/ml/72 h) in C-13 incorporation into nucleic acid ribose fro m glucose. Concomitantly, we observed a decrease in glucose oxidation and t he synthesis of glutamate, palmitate and stearate from glucose. Our results demonstrate that this organophosphate pesticide exerts a leukemogenic effe ct by the recruitment of glucose carbons for nucleic acid synthesis thus pr omoting proliferation simultaneous with poor differentiation. The imbalance d 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 phe notype observed in TGF-beta treated lung epithelial carcinoma cells. (C) 20 01 Elsevier Science Ltd. All rights reserved.