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.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Merlo Domenico Franco, Agramunt Silvia, Anna Lívia, Besselink Harrie, Botsivali Maria, Brady Nigel J, Ceppi Marcello, Chatzi Leda, Chen Bowang, Decordier Ilse, Farmer Peter B, Fleming Sarah, Fontana Vincenzo, Försti Asta, Fthenou Eleni, Gallo Fabio, Georgiadis Panagiotis, Gmuender Hans, Godschalk Roger W, Granum Berit, Hardie Laura J, Hemminki Kari, Hochstenbach Kevin, Knudsen Lisbeth E, Kogevinas Manolis, Kovács Katalin, Kyrtopoulos Soterios A, Løvik Martinus, Nielsen Jeanette K, Nygaard Unni Cecilie, Pedersen Marie, Rydberg Per, Schoket Bernadette, Segerbäck Dan, Singh Rajinder, Sunyer Jordi, Törnqvist Margareta, van Loveren Henk, van Schooten Frederik J, Vande Loock Kim, von Stedingk Hans, Wright John, Kleinjans Jos C, Kirsch-Volders Micheline, van Delft Joost H M, NewGeneris Consortium
Аннотация
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.