Low concentrations of permethrin and malathion induce numerical and structural abnormalities in KMT2A and IGH genes in vitro

J Appl Toxicol. 2018 Sep;38(9):1262-1270. doi: 10.1002/jat.3638. Epub 2018 May 9.

Abstract

Pesticides are commonly used worldwide and almost every human is potentially exposed to these chemicals. Exposure to pesticides such as permethrin and malathion has been associated with hematological malignancies in epidemiological studies. However, biological evidence showing if these chemicals induce genetic aberrations involved in the etiology of leukemia and lymphoma is missing. In our previous work, we have shown that a single high exposure (200 μm, 24 hours) of permethrin and malathion induce damage in genes associated with hematological malignancies in peripheral blood mononuclear cells analyzed by interphase fluorescence in situ hybridization (FISH). In the present study, we assessed by FISH whether exposure to low concentrations (0.1 μm, 72 hours) of permethrin and malathion induce aberrations in KMT2A and IGH genes, which are involved in the etiology of leukemia and lymphoma. Peripheral blood mononuclear cells were exposed to the chemicals, and damage in these genes was assessed on interphases and metaphases. We observed that both chemicals at low concentration induced structural aberrations in KMT2A and IGH genes. A higher level of damage was observed in KMT2A gene with malathion treatment and in IGH gene with permethrin exposure. We also observed numerical aberrations induced by these chemicals. The most frequent aberrations detected on interphase FISH were also observed on metaphases. Our results show that permethrin and malathion induce genetic damage in genes associated with hematological cancer, at concentrations biologically relevant. In addition, damage was observed on dividing cells, which suggests that these cells maintain their proliferation capacity in spite of the genetic damage they possess.

Keywords: IGH; KMT2A; MLL; insecticides; leukemia; lymphoma; malathion; permethrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Cell Survival
  • Cell Transformation, Neoplastic / chemically induced
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Cells, Cultured
  • DNA Damage*
  • Dose-Response Relationship, Drug
  • Genes, Immunoglobulin Heavy Chain*
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Insecticides / toxicity*
  • Interphase
  • Leukemia / chemically induced*
  • Leukemia / enzymology
  • Leukemia / genetics
  • Leukemia / pathology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / enzymology
  • Leukocytes, Mononuclear / pathology
  • Lymphoma / chemically induced*
  • Lymphoma / enzymology
  • Lymphoma / genetics
  • Lymphoma / pathology
  • Malathion / toxicity*
  • Male
  • Metaphase
  • Mitotic Index
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Permethrin / toxicity*
  • Risk Assessment

Substances

  • Insecticides
  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Permethrin
  • Histone-Lysine N-Methyltransferase
  • Malathion