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

Pediatr Blood Cancer. 2007 Oct 15;49(5):624-8. doi: 10.1002/pbc.21283.

Abstract

Background: 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).

Procedure: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chromosomes, Human, Pair 21*
  • Chromosomes, Human, Pair 8*
  • Female
  • Fetal Blood
  • Fetus
  • Humans
  • Infant, Newborn
  • Leukemia / etiology*
  • Leukemia / genetics
  • Maternal Exposure / adverse effects
  • Meconium / chemistry
  • Pesticides / analysis
  • Pregnancy
  • Propoxur / analysis*
  • Translocation, Genetic*

Substances

  • Pesticides
  • Propoxur