PMID- 29741206
OWN - NLM
STAT- MEDLINE
DCOM- 20191025
LR  - 20191025
IS  - 1099-1263 (Electronic)
IS  - 0260-437X (Linking)
VI  - 38
IP  - 9
DP  - 2018 Sep
TI  - Low concentrations of permethrin and malathion induce numerical and structural 
      abnormalities in KMT2A and IGH genes in vitro.
PG  - 1262-1270
LID - 10.1002/jat.3638 [doi]
AB  - 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 mum, 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 mum, 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.
CI  - Copyright (c) 2018 John Wiley & Sons, Ltd.
FAU - Navarrete-Meneses, M P
AU  - Navarrete-Meneses MP
AUID- ORCID: 0000-0002-2686-4101
AD  - Laboratorio de Genetica y Cancer, Departamento de Genetica Humana, Instituto 
      Nacional de Pediatria, Ciudad de Mexico, Mexico.
AD  - Posgrado en Ciencias Biologicas, Universidad Nacional Autonoma de Mexico, Ciudad 
      de Mexico, Mexico.
FAU - Pedraza-Melendez, A I
AU  - Pedraza-Melendez AI
AD  - Laboratorio de Genetica y Cancer, Departamento de Genetica Humana, Instituto 
      Nacional de Pediatria, Ciudad de Mexico, Mexico.
FAU - Salas-Labadia, C
AU  - Salas-Labadia C
AUID- ORCID: 0000-0002-3301-7357
AD  - Laboratorio de Genetica y Cancer, Departamento de Genetica Humana, Instituto 
      Nacional de Pediatria, Ciudad de Mexico, Mexico.
FAU - Moreno-Lorenzana, D
AU  - Moreno-Lorenzana D
AUID- ORCID: 0000-0003-3029-4241
AD  - Catedra CONACYT-Instituto Nacional de Pediatria, Mexico.
FAU - Perez-Vera, P
AU  - Perez-Vera P
AUID- ORCID: 0000-0001-5662-6991
AD  - Laboratorio de Genetica y Cancer, Departamento de Genetica Humana, Instituto 
      Nacional de Pediatria, Ciudad de Mexico, Mexico.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180509
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (Insecticides)
RN  - 0 (KMT2A protein, human)
RN  - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
RN  - 509F88P9SZ (Permethrin)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - U5N7SU872W (Malathion)
SB  - IM
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Cell Transformation, Neoplastic/chemically induced/genetics/metabolism/pathology
MH  - Cells, Cultured
MH  - *DNA Damage
MH  - Dose-Response Relationship, Drug
MH  - *Genes, Immunoglobulin Heavy Chain
MH  - Histone-Lysine N-Methyltransferase/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Insecticides/*toxicity
MH  - Interphase
MH  - Leukemia/*chemically induced/enzymology/genetics/pathology
MH  - Leukocytes, Mononuclear/*drug effects/enzymology/pathology
MH  - Lymphoma/*chemically induced/enzymology/genetics/pathology
MH  - Malathion/*toxicity
MH  - Male
MH  - Metaphase
MH  - Mitotic Index
MH  - Myeloid-Lymphoid Leukemia Protein/*genetics
MH  - Permethrin/*toxicity
MH  - Risk Assessment
OTO - NOTNLM
OT  - IGH
OT  - KMT2A
OT  - MLL
OT  - insecticides
OT  - leukemia
OT  - lymphoma
OT  - malathion
OT  - permethrin
EDAT- 2018/05/10 06:00
MHDA- 2019/10/28 06:00
CRDT- 2018/05/10 06:00
PHST- 2018/02/01 00:00 [received]
PHST- 2018/03/22 00:00 [revised]
PHST- 2018/03/30 00:00 [accepted]
PHST- 2018/05/10 06:00 [pubmed]
PHST- 2019/10/28 06:00 [medline]
PHST- 2018/05/10 06:00 [entrez]
AID - 10.1002/jat.3638 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2018 Sep;38(9):1262-1270. doi: 10.1002/jat.3638. Epub 2018 May 9.