Association between prenatal pesticide exposures and the generation of leukemia‐associated T(8;21)

Abstract

This study was designed to investigate the relationship between prenatal pesticide exposures and the generation of leukemia-associated t(8;21)(q22;q22), one of the most common cytogenetic abnormalities in childhood acute myeloid leukemia (AML). Gas chromatography/mass spectrometry (GC/MS) was used to quantitatively detect different pesticides (propoxur and cypermethrin) in meconium from 49 newborn babies from the Philippines. The generation of t(8;21) was determined in the corresponding umbilical cord blood samples by detection of the AML1-ETO fusion transcripts derived from t(8;21) using nested RT-PCR. Levels for the AML1-ETO fusion transcripts were quantitated by real-time RT-PCR in the t(8;21) positive cord blood samples. AML1-ETO fusion transcript forms were characterized by RT-PCR amplification and DNA sequencing. In the present study using umbilical cord blood samples obtained from infants whose prenatal exposure to the pesticide, propoxur, was determined by meconium analysis, we showed that (i) incidence of t(8;21) in the exposed group was two-fold higher than that in the unexposed group; and (ii) the levels for AML1-ETO fusion transcripts resulting from t(8;21) positively correlated with propoxur concentrations in meconium. Similar heterogeneity in the fusion transcripts was detected in the t(8;21) positive cord blood samples as in our previous study with t(8;21) AML patients. These results further confirm the prenatal origin of t(8;21) and establish a significant correlation between prenatal pesticide exposures and the generation of t(8;21). They suggest that prenatal pesticide exposures may be causal factors for the generation of leukemia-associated chromosomal translocations.