Merlo, D. F., Agramunt, S., Anna, L., Besselink, H., Botsivali, M., Brady, N. J., Ceppi, M., Chatzi, L., Chen, B., Decordier, I., Farmer, P. B., Fleming, S., Fontana, V., Försti, A., Fthenou, E., Gallo, F., Georgiadis, P., Gmuender, H., Godschalk, R. W., ... NewGeneris Consortium (2014). 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. Environmental Health Perspectives, 122(2), 193-200. https://doi.org/10.1289/ehp.1206324
Merlo, DF, Agramunt, S, Anna, L, Besselink, H, Botsivali, M, Brady, NJ, Ceppi, M, Chatzi, L, Chen, B, Decordier, I, Farmer, PB, Fleming, S, Fontana, V, Försti, A, Fthenou, E, Gallo, F, Georgiadis, P, Gmuender, H, Godschalk, RW, Granum, B, Hardie, LJ, Hemminki, K, Hochstenbach, K, Knudsen, LE, Kogevinas, M, Kovács, K, Kyrtopoulos, SA, Løvik, M, Nielsen, JK, Nygaard, UC, Pedersen, M, Rydberg, P, Schoket, B, Segerbäck, D, Singh, R, Sunyer, J, Törnqvist, M, van Loveren, H, van Schooten, FJ, Vande Loock, K, von Stedingk, H, Wright, AJ, Kleinjans, JC, Kirsch-Volders, M, van Delft, JHM & NewGeneris Consortium 2014, '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', Environmental Health Perspectives, vol. 122, no. 2, pp. 193-200. https://doi.org/10.1289/ehp.1206324
@article{110a85bcbf6249a09a11200f920b6aad,
title = "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",
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 (M1dG) 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 M1dG-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{\textregistered} (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX{\textregistered} (for estrogens) (2 genes), and DR CALUX{\textregistered} (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.",
author = "Merlo, {Domenico Franco} and Silvia Agramunt and L{\'i}via Anna and Harrie Besselink and Maria Botsivali and Brady, {Nigel J} and Marcello Ceppi and Leda Chatzi and Bowang Chen and Ilse Decordier and Farmer, {Peter B} and Sarah Fleming and Vincenzo Fontana and Asta F{\"o}rsti and Eleni Fthenou and Fabio Gallo and Panagiotis Georgiadis and Hans Gmuender and Godschalk, {Roger W} and Berit Granum and Hardie, {Laura J} and Kari Hemminki and Kevin Hochstenbach and Knudsen, {Lisbeth E} and Manolis Kogevinas and Katalin Kov{\'a}cs and Kyrtopoulos, {Soterios A} and Martinus L{\o}vik and Nielsen, {Jeanette K} and Nygaard, {Unni Cecilie} and Marie Pedersen and Per Rydberg and Bernadette Schoket and Dan Segerb{\"a}ck and Rajinder Singh and Jordi Sunyer and Margareta T{\"o}rnqvist and {van Loveren}, Henk and {van Schooten}, {Frederik J} and {Vande Loock}, Kim and {von Stedingk}, Hans and Wright, {Andrew John} and Kleinjans, {Jos C} and Micheline Kirsch-Volders and {van Delft}, {Joost H M} and {NewGeneris Consortium}",
year = "2014",
month = feb,
doi = "10.1289/ehp.1206324",
language = "English",
volume = "122",
pages = "193--200",
journal = "Environmental Health Perspectives",
issn = "0091-6765",
publisher = "National Institute of Environmental Health Sciences",
number = "2",
}
TY - JOUR
T1 - Micronuclei in cord blood lymphocytes and associations with biomarkers of exposure to carcinogens and hormonally active factors, gene polymorphisms, and gene expression
T2 - the NewGeneris cohort
AU - Merlo, Domenico Franco
AU - Agramunt, Silvia
AU - Anna, Lívia
AU - Besselink, Harrie
AU - Botsivali, Maria
AU - Brady, Nigel J
AU - Ceppi, Marcello
AU - Chatzi, Leda
AU - Chen, Bowang
AU - Decordier, Ilse
AU - Farmer, Peter B
AU - Fleming, Sarah
AU - Fontana, Vincenzo
AU - Försti, Asta
AU - Fthenou, Eleni
AU - Gallo, Fabio
AU - Georgiadis, Panagiotis
AU - Gmuender, Hans
AU - Godschalk, Roger W
AU - Granum, Berit
AU - Hardie, Laura J
AU - Hemminki, Kari
AU - Hochstenbach, Kevin
AU - Knudsen, Lisbeth E
AU - Kogevinas, Manolis
AU - Kovács, Katalin
AU - Kyrtopoulos, Soterios A
AU - Løvik, Martinus
AU - Nielsen, Jeanette K
AU - Nygaard, Unni Cecilie
AU - Pedersen, Marie
AU - Rydberg, Per
AU - Schoket, Bernadette
AU - Segerbäck, Dan
AU - Singh, Rajinder
AU - Sunyer, Jordi
AU - Törnqvist, Margareta
AU - van Loveren, Henk
AU - van Schooten, Frederik J
AU - Vande Loock, Kim
AU - von Stedingk, Hans
AU - Wright, Andrew John
AU - Kleinjans, Jos C
AU - Kirsch-Volders, Micheline
AU - van Delft, Joost H M
AU - NewGeneris Consortium
PY - 2014/2
Y1 - 2014/2
N2 - 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 (M1dG) 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 M1dG-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® (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX® (for estrogens) (2 genes), and DR CALUX® (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.
AB - 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 (M1dG) 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 M1dG-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® (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX® (for estrogens) (2 genes), and DR CALUX® (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.
U2 - 10.1289/ehp.1206324
DO - 10.1289/ehp.1206324
M3 - Journal article
C2 - 24252472
SN - 0091-6765
VL - 122
SP - 193
EP - 200
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
IS - 2
ER -
