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Increased frequency of specific genomic deletions resulting from in vitro malathion exposure
J M Pluth1, J A Nicklas, J P O'Neill
1Genetics Laboratory, University of Vermont, Burlington, 05401, USA.
Abstract:
Malathion is a widely used pesticide with high potential for human exposure. Epidemiological studies suggest that individuals with chronic environmental exposures to pesticides have increased risks of various hematological malignancies. The genotoxic data to date have been somewhat inconclusive with regard to malathion exposure. We have used a cell cloning assay to study the genotoxicity of in vitro exposure of human T lymphocytes to malathion. We exposed cells in G0 to doses of malathion ranging from 10 to 600 microg/ml. Mutant frequencies of treated samples showed both intra- and interindividual variability and, in some cases, slight significant increases over the controls. Molecular analysis of hprt mutants resulting from both in vitro and an in vivo malathion exposure was performed by genomic multiplex PCR. In seven in vitro experiments (using cells from four different individuals) and one experiment on an individual exposed in vivo, one or more independent mutant(s) containing a partial deletion of exon 3 have been isolated from each individual. In five of the seven mutants, the deleted regions overlap extensively, revealing an area within exon 3 exceptionally prone to deletions upon exposure to malathion, This work provides the first evidence of an association between malathion exposure and specific mutations in human T lymphocytes. Additional work is necessary to determine the underlying molecular mechanism for these deletions and how this may relate to agricultural workers' increased risk of cancer.
Insights
Malathion pesticide exposure may cause specific mutations in human T lymphocytes. This study found deletions in exon 3, suggesting a link between malathion and genotoxicity in agricultural workers.
Area of Science:
- Environmental Toxicology
- Genetics
- Molecular Biology
Background:
- Malathion is a common pesticide with significant human exposure potential.
- Epidemiological studies link chronic pesticide exposure to increased risks of hematological malignancies.
- Existing genotoxicity data for malathion is inconclusive.
Purpose of the Study:
- To investigate the genotoxicity of malathion exposure in human T lymphocytes.
- To identify specific mutations induced by malathion in vitro and in vivo.
- To explore the potential link between malathion exposure and cancer risk in agricultural workers.
Main Methods:
- Utilized a cell cloning assay to assess malathion genotoxicity in human T lymphocytes.
- Exposed cells to varying doses of malathion (10–600 microg/ml) in the G0 phase.
- Performed molecular analysis of hprt mutants using genomic multiplex PCR for both in vitro and in vivo exposures.
Main Results:
- Malathion exposure showed slight, significant increases in mutant frequencies in some cases.
- Identified independent mutants with partial exon 3 deletions in both in vitro and in vivo exposures.
- Discovered overlapping deletion regions within exon 3, indicating a malathion-sensitive site.
Conclusions:
- This study provides the first evidence linking malathion exposure to specific mutations in human T lymphocytes.
- The findings suggest malathion can induce deletions in a specific region of exon 3.
- Further research is needed to elucidate the molecular mechanisms and implications for agricultural worker cancer risk.