Chromosomal aberrations in human lymphocytes exposed to the anticholinesterase pesticide isofenphos with mechanisms of leukemogenesis

Leukemia Research
Robert D WilliamsThomas R Eggers

Abstract

Human lymphocytes were exposed to the leukemogenic pesticide isofenphos (IFP) to investigate its effects on chromosomal DNA and cholinergic homeostasis using cholinesterase activity as a marker. Isolated peripheral lymphocytes were administered concentrations of IFP ranging from 0.1 ng/ml to 10 microg/ml. The absence (Group 1) and presence (Group 2) of DNA repair inhibitors 4 mM hydroxyurea (HU), 40 microM cytosine arabinoside (ARA-C) and an NADPH regenerating system (NRS) (Group 3) were analyzed at 1, 6 and 24 h by single cell gel electrophoresis using the comet assay. Significant damage to DNA directly from IFP at 1 h by remarkably low concentrations was observed in Group 1, escalating in Group 2 with DNA repair inhibition, while Group 3 disruptions were highest due to the presence of the NRS P-450 microsomal fraction conducive to producing reactive IFP-oxon and N-desalkyl metabolites. The extent of DNA aberrations increased further in parallel within the groups at 6 and 24 h. Male and female chemical sensitivities were similar on average (P < 0.01). Cholinesterase activity measured in a satellite group was inhibited with 0.1 microg/ml IFP by 69, 62, and 48% at 1, 6, and 24 h, respectively, indicating gradual induction of com...Continue Reading

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Citations

Apr 7, 2010·Environmental Science and Pollution Research International·Hédi Ben MansourLeila Chekir-Ghedira
Feb 22, 2012·Environmental Science and Pollution Research International·Hedi Ben MansourLeila Chekir-Ghedira
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