Abstract |
Introduction: The potential adverse effects of environmental chemicals on children’s
health and development are a matter of widespread public health concern. Persistent organic
pollutants (POPs) bioaccumulate through the food chain and human exposure to POPs has
been associated with certain cancers in adults and children. Micronuclei (MN) are
extranuclear small nuclei caused by DNA damage, serve as markers of pre-carcinogenic
events and have been associated with cancer risk in adults but data on MN frequency in
children are limited. Our aim was to investigate for the first time the association between in
utero exposure to POPs with MN frequency in lymphocytes of preschool children from the
Rhea mother-child cohort in Crete, Greece (n=328).
Methods: Concentrations of several polychlorinated biphenyls (PCBs),
dichlorodiphenyltrichloroethane (DDT)/dichlorodiphenyldichloroethylene (DDE), and
hexachlorobenzene (HCB) were determined in first trimester maternal serum by triple
quadrupole mass spectrometry. We used the cytokinesis-block micronucleus assay to assess
MN frequencies in 1000 binucleated T-lymphocytes (MNBN) in children at 4 years of
age.Negative binomial regression models were used to estimate associations between POP
concentrations during pregnancy and MN frequencies in childhood.
Results: Geometric mean DDE, HCB and PCBs serum concentrations in pregnant
women were 1960.1 pg/ml, 87.7 pg/ml and 329.9 pg/ml respectively. On multivariable
regression analyses, a 10-fold increase in DDE levels in pregnancy was associated with
increased risk of micronuclei formation after adjusting for mother’s age, parity, child’s sex,
pre-pregnancy BMI, mother’s educational level, passive smoking, smoking during early
pregnancy and breastfeeding duration, maternal serum levels of triglycerides and total
cholesterol (IRR 1.47 95% CI: 1.05, 2.06). Respectively a 10 fold increase in PCBs levels
was associated with increased risk (IRR 2.56 95% CI: 1.34, 4.91). Prenatal exposure to HCB
was not associated with the risk of micronuclei frequencies. Clear monotonic exposure–
response patterns were apparent for DDE and dioxin like PCBs.
Conclusion: These findings suggest that exposure to DDE and PCBs during
pregnancy may increase the risk of micronuclei frequency in children. This is the first study to
present prenatal POPs exposures and MN formation in later life and further studies are needed
to confirm these findings and examine the biological mechanisms underlying the observed
associations. Further follow up of this cohort will allow determining if prenatal exposure to
POPs has, in addition, an effect on genetoxicity in late childhood and also long term
carcinogenic risks.
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