INCREASED FREQUENCY OF SPECIFIC GENOMIC DELETIONS RESULTING FROM IN-VITRO MALATHION EXPOSURE

Malathion is a widely used pesticide with high potential for human exp osure. Epidemiological studies suggest that individuals with chronic e nvironmental exposures to pesticides have increased risks of various h ematological malignancies. The genotoxic data to date have been somewh at 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 G(0), to doses of mal athion ranging from 10 to 600 mu g/ml. Mutant frequencies of treated s amples showed both intra- and interindividual variability and, in some cases, slight significant increases over the controls. Molecular anal ysis of hprt mutants resulting from both in vitro and an in vivo malat hion exposure was performed by genomic multiplex PCR. In seven in vitr o experiments (using cells from four different individuals) and one ex periment on an individual exposed in vivo, one or more independent mut ant(s) containing a partial deletion of exon 3 have been Isolated from each individual. In five of the seven mutants, the deleted regions ov erlap 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 mu tations in human T lymphocytes. Additional work is necessary to determ ine the underlying molecular mechanism for these deletions and how thi s may relate to agricultural workers' increased risk of cancer.