title: Increased frequency of specific genomic deletions resulting from in vitro malathion exposure.
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.
authors.affiliation: Genetics Laboratory, University of Vermont, Burlington, 05401, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Pluth
authors.forename: J A
authors.initials: JA
authors.lastname: Nicklas
authors.forename: J P
authors.initials: JP
authors.lastname: O'Neill
authors.forename: R J
authors.initials: RJ
authors.lastname: Albertini
mesh_terms: D000328:Adult; D001483:Base Sequence; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004340:Drug Contamination; D004351:Drug Resistance / Q000235:genetics; D005091:Exons / Q000187:drug effects; D005796:Genes / Q000187:drug effects*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008294:Malathion / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009690:Nucleic Acid Conformation; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D016192:Resting Phase, Cell Cycle; D017384:Sequence Deletion / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*; D013866:Thioguanine / Q000494:pharmacology
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine; D008294:Malathion