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Using Caenorhabditis elegans for Studying Trans- and Multi-Generational Effects of Toxicants
Published on: July 29, 2019
"Exposure to the insecticides permethrin and malathion induces leukemia and lymphoma-associated gene aberrations in
M P Navarrete-Meneses1, C Salas-Labadía2, M Sanabrais-Jiménez2
1Laboratorio de Genética y Cáncer, Departamento de Genética Humana, Instituto Nacional de Pediatría, Insurgentes Sur 3700 Letra C. Delegación Coyoacán, CP 04530 Ciudad de México, Mexico; Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Av. Ciudad Universitaria 3000, C.P. 04510, Coyoacán, Ciudad de México, Mexico.
Abstract:
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.
Insights
Exposure to permethrin and malathion insecticides can damage cancer genes. This study found these chemicals induce genetic aberrations and fusions linked to leukemia and lymphoma, highlighting potential risks.
Area of Science:
- Environmental toxicology
- Molecular genetics
- Hematological oncology
Background:
- Epidemiological studies link permethrin and malathion exposure to increased risks of leukemia and lymphoma.
- Understanding the genotoxic mechanisms of these insecticides is crucial for assessing hematological malignancy risk.
Purpose of the Study:
- To investigate the in vitro genotoxic effects of permethrin and malathion on genes critical to hematological malignancies.
- To determine if these insecticides induce chromosomal aberrations and gene fusions in relevant cell types.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) and K562 cells were exposed to permethrin and malathion in vitro.
- Fluorescence in situ hybridization (FISH) was used to detect aneuploidy and structural gene alterations (IGH, KMT2A, ETV6, RUNX1).
- Nested reverse transcription polymerase chain reaction (RT-PCR) identified specific gene fusions (IGH-BCL2, KMT2A-AFF1, ETV6-RUNX1).
Main Results:
- Permethrin exposure induced aneuploidy and structural alterations in IGH and KMT2A genes.
- Malathion exposure induced breaks in the KMT2A gene.
- Both insecticides induced gene fusions (ETV6-RUNX1, IGH-BCL2, KMT2A-AFF1) in a dose- and time-dependent manner.
- Permethrin also induced the ETV6-RUNX1 fusion in PBMCs.
Conclusions:
- Permethrin and malathion cause direct genotoxic damage to critical cancer genes.
- The observed genetic aberrations and fusions provide a mechanistic link between insecticide exposure and hematological malignancies.
- This study underscores the potential carcinogenic risk associated with these commonly used insecticides.
