Get access

Pesticide induced alterations in marrow physiology and depletion of stem and stromal progenitor population: An experimental model to study the toxic effects of pesticide

Authors

  • Sumanta Chatterjee,

    1. Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta-700073, India
    Search for more papers by this author
  • Pratima Basak,

    1. Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta-700073, India
    Search for more papers by this author
  • Malay Chaklader,

    1. Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta-700073, India
    Search for more papers by this author
  • Prosun Das,

    1. Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta-700073, India
    Search for more papers by this author
  • Jacintha Archana Pereira,

    1. Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta-700073, India
    Search for more papers by this author
  • Samaresh Chaudhuri,

    1. Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta-700073, India
    Search for more papers by this author
  • Sujata Law

    Corresponding author
    1. Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta-700073, India
    • Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta-700073, India. E-mail: sujatalaw369369@gmail.com sumc83@gmail.com Phone No. 09051259521

    Search for more papers by this author

Abstract

Long-term exposure of agriculturally used organochloride and organophosphate pesticides have been shown to cause long-lasting hematotoxicity and increased incidence of aplastic anemia in humans. The mechanisms involved in pesticide induced hematotoxicity and the features of toxicity that may play a major role in bone marrow suppression are not known. The aim of the present study was to investigate the hematological consequences of pesticide exposure in swiss albino mice exposed to aqueous mixture of common agriculturally used pesticides for 6 h/day, 5 days/week for 13 weeks. After the end of last exposure, without a recovery period, the strong hematotoxic effect of pesticide was assessed in mice with long-term bone marrow explant culture (LTBMC-Ex) system and cell colony forming assays. Bone marrow explant culture from the pesticide exposed group of mice failed to generate a supportive stromal matrix and did not produce adequate number of hematopoietic cells and found to contain largely the adipogenic precursors. The decreased cell colony numbers in the pesticide exposed group indicated defective maturational and functional status of different marrow cell lineages. As a whole, exposure of mice to the mixture of pesticides reduced the total number of bone marrow cells (granulocytes are the major targets of pesticide toxicity), hematopoietic, and non-hematopoietic progenitor cells and most of the hematological parameters. Replication of primitive stem/progenitor cells in the marrow was decreased following pesticide exposure with G0/G1-phase arrest of most of the cells. The progenitor cells showed decreased percentage of cells in S/G2/M-phase. The increased apoptosis profile of the marrow progenitors (Increased CD95 expression) and primitive stem cells (High Annexin-V positivity on Sca1+ cells) with an elevated intracellular cleaved caspase-3 level on the Sca1+ bone marrow cells provided the base necessary for explaining the deranged bone marrow microenvironmental structure which was evident from scanning electron micrographs. These results clearly indicate a strong, long lasting toxic effect of pesticides on the bone marrow microenvironment and different microenvironmental components which ultimately leads to the formation of a degenerative disease like aplastic anemia. © 2011 Wiley Periodicals, Inc. Environ Toxicol 29: 84–97, 2014.

Get access to the full text of this article

Ancillary