Exposure to the insecticides permethrin and malathion induces leukemia and lymphoma-associated gene aberrations in vitro

Epidemiological studies have associated the exposure to permethrin and malathion with increased risk of leukemia and lymphoma. The aim of this study was to evaluate whether in vitro exposure to permethrin and malathion induces aberrations in genes involved in the etiology of these hematological mali...

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Veröffentlicht in:Toxicology in vitro 2017-10, Vol.44, p.17-26
Hauptverfasser: Navarrete-Meneses, M.P., Salas-Labadía, C., Sanabrais-Jiménez, M., Santana-Hernández, J., Serrano-Cuevas, A., Juárez-Velázquez, R., Olaya-Vargas, A., Pérez-Vera, P.
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container_title Toxicology in vitro
container_volume 44
creator Navarrete-Meneses, M.P.
Salas-Labadía, C.
Sanabrais-Jiménez, M.
Santana-Hernández, J.
Serrano-Cuevas, A.
Juárez-Velázquez, R.
Olaya-Vargas, A.
Pérez-Vera, P.
description Epidemiological studies have associated the exposure to permethrin and malathion with increased risk of leukemia and lymphoma. The aim of this study was to evaluate whether in vitro exposure to permethrin and malathion induces aberrations in genes involved in the etiology of these hematological malignancies. Genetic abnormalities in the IGH, KMT2A (MLL), ETV6 and RUNX1 genes, and aneuploidy induced by the in vitro exposure to permethrin and malathion (200μM, 24h), were analyzed by FISH in peripheral blood mononuclear cells (PBMCs). The gene fusions IGH-BCL2, KMT2A-AFF1 and ETV6-RUNX1 were further analyzed with nested RT-PCR in PBMCs, and in K562 cells exposed to acute and chronic treatments (0.1μM, 24h or every third day for two weeks) of insecticides. FISH analysis revealed that permethrin induces aneuploidy and structural alterations in IGH and KMT2A genes, and malathion induces breaks in KMT2A. RT-PCR detected ETV6-RUNX1 fusion in PBMCs acutely exposed to permethrin. Permethrin also induced ETV6-RUNX1 and IGH-BCL2 fusions in K562 cells, and malathion induced KMT2A-AFF1 and ETV6-RUNX1 fusions. Overall, we identified that both insecticides induce breaks and fusions in the studied genes, and permethrin induces aneuploidy. This study presents evidence of damage in cancer genes caused by these insecticides. •Permethrin induces breaks in KMT2A and IGH genes in peripheral blood mononuclear cells (PBMCs) exposed in vitro.•Permethrin induces aneuploidy in PBMCs exposed in vitro.•Malathion induces KMT2A breaks in PBMCs exposed in vitro.•Permethrin and malathion induced oncogenic fusions in PBMCs and K562 cells.
doi_str_mv 10.1016/j.tiv.2017.06.013
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This study presents evidence of damage in cancer genes caused by these insecticides. •Permethrin induces breaks in KMT2A and IGH genes in peripheral blood mononuclear cells (PBMCs) exposed in vitro.•Permethrin induces aneuploidy in PBMCs exposed in vitro.•Malathion induces KMT2A breaks in PBMCs exposed in vitro.•Permethrin and malathion induced oncogenic fusions in PBMCs and K562 cells.</description><identifier>ISSN: 0887-2333</identifier><identifier>EISSN: 1879-3177</identifier><identifier>DOI: 10.1016/j.tiv.2017.06.013</identifier><identifier>PMID: 28624474</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Abnormalities ; Aneuploidy ; Cancer ; Cell Survival - drug effects ; Cells, Cultured ; Epidemiology ; Etiology ; Exposure ; Gene Fusion ; Genes ; Genetic abnormalities ; Heavy chains ; Hematology ; Humans ; IGH ; Immunoglobulins ; Insecticides ; Insecticides - toxicity ; K562 Cells ; KMT2A ; Leukemia ; Leukemia - genetics ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - drug effects ; Leukocytes, Mononuclear - metabolism ; Lymphoma ; Lymphoma - genetics ; Malathion ; Malathion - toxicity ; Male ; MLL ; Oncogene Proteins, Fusion - genetics ; Peripheral blood mononuclear cells ; Permethrin ; Permethrin - toxicity ; Polymerase chain reaction ; Runx1 protein</subject><ispartof>Toxicology in vitro, 2017-10, Vol.44, p.17-26</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. 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The aim of this study was to evaluate whether in vitro exposure to permethrin and malathion induces aberrations in genes involved in the etiology of these hematological malignancies. Genetic abnormalities in the IGH, KMT2A (MLL), ETV6 and RUNX1 genes, and aneuploidy induced by the in vitro exposure to permethrin and malathion (200μM, 24h), were analyzed by FISH in peripheral blood mononuclear cells (PBMCs). The gene fusions IGH-BCL2, KMT2A-AFF1 and ETV6-RUNX1 were further analyzed with nested RT-PCR in PBMCs, and in K562 cells exposed to acute and chronic treatments (0.1μM, 24h or every third day for two weeks) of insecticides. FISH analysis revealed that permethrin induces aneuploidy and structural alterations in IGH and KMT2A genes, and malathion induces breaks in KMT2A. RT-PCR detected ETV6-RUNX1 fusion in PBMCs acutely exposed to permethrin. Permethrin also induced ETV6-RUNX1 and IGH-BCL2 fusions in K562 cells, and malathion induced KMT2A-AFF1 and ETV6-RUNX1 fusions. Overall, we identified that both insecticides induce breaks and fusions in the studied genes, and permethrin induces aneuploidy. This study presents evidence of damage in cancer genes caused by these insecticides. •Permethrin induces breaks in KMT2A and IGH genes in peripheral blood mononuclear cells (PBMCs) exposed in vitro.•Permethrin induces aneuploidy in PBMCs exposed in vitro.•Malathion induces KMT2A breaks in PBMCs exposed in vitro.•Permethrin and malathion induced oncogenic fusions in PBMCs and K562 cells.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28624474</pmid><doi>10.1016/j.tiv.2017.06.013</doi><tpages>10</tpages></addata></record>
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subjects Abnormalities
Aneuploidy
Cancer
Cell Survival - drug effects
Cells, Cultured
Epidemiology
Etiology
Exposure
Gene Fusion
Genes
Genetic abnormalities
Heavy chains
Hematology
Humans
IGH
Immunoglobulins
Insecticides
Insecticides - toxicity
K562 Cells
KMT2A
Leukemia
Leukemia - genetics
Leukocytes (mononuclear)
Leukocytes, Mononuclear - drug effects
Leukocytes, Mononuclear - metabolism
Lymphoma
Lymphoma - genetics
Malathion
Malathion - toxicity
Male
MLL
Oncogene Proteins, Fusion - genetics
Peripheral blood mononuclear cells
Permethrin
Permethrin - toxicity
Polymerase chain reaction
Runx1 protein
title Exposure to the insecticides permethrin and malathion induces leukemia and lymphoma-associated gene aberrations in vitro
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