TY - JOUR
TI - 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
AU - Merlo, Domenico Franco
AU - Agramunt, Silvia
AU - Anna, Livia and
AU - Besselink, Harrie
AU - Botsivali, Maria
AU - Brady, Nigel J.
AU - Ceppi,
AU - Marcello
AU - Chatzi, Leda
AU - Chen, Bowang
AU - Decordier, Ilse and
AU - Farmer, Peter B.
AU - Fleming, Sarah
AU - Fontana, Vincenzo
AU - Foersti,
AU - Asta
AU - Fthenou, Eleni
AU - Gallo, Fabio
AU - Georgiadis, Panagiotis and
AU - Gmuender, Hans
AU - Godschalk, Roger W.
AU - Granum, Berit
AU - Hardie,
AU - Laura J.
AU - Hemminki, Kari
AU - Hochstenbach, Kevin
AU - Knudsen, Lisbeth
AU - E.
AU - Kogevinas, Manolis
AU - Kovacs, Katalin
AU - Kyrtopoulos, Soterios
AU - A.
AU - Lovik, Martinus
AU - Nielsen, Jeanette K.
AU - Nygaard, Unni
AU - Cecilie
AU - Pedersen, Marie
AU - Rydberg, Per
AU - Schoket, Bernadette and
AU - Segerback, Dan
AU - Singh, Rajinder
AU - Sunyer, Jordi
AU - Tornqvist,
AU - Margareta
AU - van Loveren, Henk
AU - van Schooten, Frederik J.
AU - vande
AU - Loock, Kim
AU - von Stedingk, Hans
AU - Wright, John
AU - Kleinjans, Jos C.
AU - and Kirsch-Volders, Micheline
AU - van Delft, Joost H. M.
AU - NewGeneris
AU - Consortium
JO - Environmental Health Perspectives
PY - 2014
VL - 122
TODO - 2
SP - 193-200
PB - US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
SN - 0091-6765, 1552-9924
TODO - 10.1289/ehp.1206324
TODO - null
TODO - 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.
ER -