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• W1989590459 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 compensatory synthesis. Restoration of cholinergic homeostasis may be exceptionally impaired at higher IFP concentrations from acetyl-CoA depletion [Leuk. Res. 25 (2001) 883]. In summary, these studies reveal that exposure to the organophosphate pesticide isofenphos induces human DNA mutation beyond endogenous repair capacity and disrupts cholinergic nuclear signaling affectively constructing the mutator phenotype of leukemogenesis." @default.
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• W1989590459 date "2004-09-01" @default.
• W1989590459 modified "2023-10-14" @default.
• W1989590459 title "Chromosomal aberrations in human lymphocytes exposed to the anticholinesterase pesticide isofenphos with mechanisms of leukemogenesis" @default.
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• W1989590459 doi "https://doi.org/10.1016/j.leukres.2003.12.014" @default.
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