Pluth J M, Nicklas J A, O'Neill J P, Albertini R J
Genetics Laboratory, University of Vermont, Burlington, 05401, USA.
Cancer Res. 1996 May 15;56(10):2393-9.
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.
马拉硫磷是一种广泛使用的杀虫剂，人类接触的可能性很高。流行病学研究表明，长期环境接触杀虫剂的个体患各种血液系统恶性肿瘤的风险增加。迄今为止，关于马拉硫磷接触的遗传毒性数据尚无定论。我们使用细胞克隆试验研究了人T淋巴细胞体外接触马拉硫磷的遗传毒性。我们将处于G0期的细胞暴露于浓度范围为10至600微克/毫升的马拉硫磷中。处理后样本的突变频率显示出个体内和个体间的变异性，在某些情况下，与对照组相比有轻微的显著增加。通过基因组多重PCR对体外和体内马拉硫磷暴露产生的hprt突变体进行分子分析。在七项体外实验（使用来自四个不同个体的细胞）和一项对体内暴露个体的实验中，从每个个体中分离出一个或多个包含外显子3部分缺失的独立突变体。在七个突变体中的五个中，缺失区域广泛重叠，揭示了外显子3内一个在接触马拉硫磷后特别容易发生缺失的区域。这项工作首次证明了马拉硫磷暴露与人类T淋巴细胞特定突变之间的关联。需要进一步的研究来确定这些缺失的潜在分子机制，以及这与农业工人患癌风险增加之间的关系。
