title: Pesticide induced marrow toxicity and effects on marrow cell population and on hematopoietic stroma.
abstract: Long term inhalation of toxic pesticides used for the domestic and industrial purposes have been shown to cause moderate to severe hematotoxicity and increased incidence of several marrow degenerative diseases, specifically hypoplastic bone marrow failure condition in humans. The progression of pesticide induced hematotoxicity and the exact underlying mechanisms of toxicity that play major role in limiting normal hematopoiesis are not quite well explained. In this present study, we have developed an animal model of hypoplastic bone marrow failure following pesticide exposure to show the deleterious effects of toxic pesticides on mouse hematopoietic system. Here we have presented the results of studying long-term marrow explant culture, IL-2, IL-3 and IL-5 receptors expression profile, fibroblast colony forming unit (CFU-F), hematopoietic progenitor cell colony formation and caspase-3 expression by the bone marrow cells. We have also identified the expression levels of several extracellular apoptosis markers (CD95/Fas) and intracellular apoptosis inducer proteins (pASK1, pJNK, caspase-3 and cleaved caspase-3) in the bone marrow cells of pesticide exposed mice. The long-term marrow explant culture demonstrated the impairment in proliferation of the stromal cells/stromal fibroblasts in culture. Decreased IL-2, IL-3 and IL-5 receptors expression profile essentially hinted at the suppressed cytokine activity in the pesticide exposed marrow. CFU-F analysis showed the defect in functional maturation of the stromal fibroblasts. The decreased hematopoietic progenitor cell colony formation indicated the toxicity induced inhibition of cellular proliferation and functional maturation of hematopoietic stem/progenitor cells in pesticide exposed marrow. We have detected a sharp increase in the expression levels of both the extracellular Fas-antigen and intracellular apoptosis inducer proteins in the bone marrow cells of pesticide exposed mice that explained well, the apoptosis pathway involved following marrow toxicity. The decreased proliferation and functional maturation of marrow stromal cells and hematopoietic progenitors with subsequent increase in marrow cellular apoptosis following pesticide toxicity provided the base necessary for explaining the increased incidence of hypoplastic bone marrow failure in humans exposed to moderate to high concentrations of pesticides.
authors: Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta 700073, India.
authors: Sumanta
authors: S
authors: Chatterjee
authors: Pratima
authors: P
authors: Basak
authors: Malay
authors: M
authors: Chaklader
authors: Prosun
authors: P
authors: Das
authors: Jacintha Archana
authors: JA
authors: Pereira
authors: Samaresh
authors: S
authors: Chaudhuri
authors: Sujata
authors: S
authors: Law
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D018929:Cell Culture Techniques; D004390:Chlorpyrifos / Q000633:toxicity*; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007306:Insecticides / Q000633:toxicity*; D051379:Mice; D011722:Pyrethrins / Q000633:toxicity*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis; D053649:Receptors, Interleukin-5 / Q000096:biosynthesis
chemical_list: D007306:Insecticides; D011722:Pyrethrins; D015375:Receptors, Interleukin-2; D016185:Receptors, Interleukin-3; D053649:Receptors, Interleukin-5; C017160:cypermethrin; D004390:Chlorpyrifos