Micronuclei in Cord Blood Lymphocytes and Associations with Biomarkers of Exposure to Carcinogens and Hormonally Active Factors, Gene Polymorphisms, and Gene Expression: The NewGeneris Cohort

Research output: Contribution to journalArticle

Abstract

Background: Leukemia incidence has increased in recent decades among European children, -suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M(1)dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M(1)dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX (R) (chemically activated luciferase expression for androgens) (8 genes), ER alpha CALUX (R) (for estrogens) (2 genes), and DR CALUX (R) (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/ 2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research.

Details

Authors
  • Domenico Franco Merlo
  • Silvia Agramunt
  • Livia Anna
  • Harrie Besselink
  • Maria Botsivali
  • Nigel J. Brady
  • Marcello Ceppi
  • Leda Chatzi
  • Bowang Chen
  • Ilse Decordier
  • Peter B. Farmer
  • Sarah Fleming
  • Vincenzo Fontana
  • Eleni Fthenou
  • Fabio Gallo
  • Panagiotis Georgiadis
  • Hans Gmuender
  • Roger W. Godschalk
  • Berit Granum
  • Laura J. Hardie
  • Kari Hemminki
  • Kevin Hochstenbach
  • Lisbeth E. Knudsen
  • Manolis Kogevinas
  • Katalin Kovacs
  • Soterios A. Kyrtopoulos
  • Martinus Lovik
  • Jeanette K. Nielsen
  • Unni Cecilie Nygaard
  • Marie Pedersen
  • Per Rydberg
  • Bernadette Schoket
  • Dan Segerback
  • Rajinder Singh
  • Jordi Sunyer
  • Margareta Tornqvist
  • Henk van Loveren
  • Frederik J. van Schooten
  • Kim vande Loock
  • Hans von Stedingk
  • John Wright
  • Jos C. Kleinjans
  • Micheline Kirsch-Volders
  • Joost H. M. van Delft
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Environmental Health and Occupational Health
Original languageEnglish
Pages (from-to)193-200
JournalEnvironmental Health Perspectives
Volume122
Issue number2
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes

Total downloads

No data available