0000000000193489
AUTHOR
Pascal Phrakonkham
Dietary exposure in utero and during lactation to a mixture of genistein and an anti-androgen fungicide in a rat mammary carcinogenesis model
Endocrine disruptors may play substantial roles in the high incidence of breast cancer. We previously described how early exposure to the mixture of phytoestrogen genistein (G) and the anti-androgen vinclozolin (V) affects peripubertal mammary development. This study evaluates the carcinogenic potential of exposure to V alone or associated with G from conception until weaning in Wistar rats. Dams were exposed to V, G or GV during pregnancy/lactation. At PND50 offspring were treated with DMBA[7,12-dimethylbenz(a)anthracene]. V or GV maternal exposure decreased number of DMBA-induced mammary tumors in the offspring, without significant modifications in tumor incidence, multiplicity and latenc…
Isoflavonoid-based bone-sparing treatments exert a low activity on reproductive organs and on hepatic metabolism of estradiol in ovariectomized rats
International audience; The use of soy isoflavones is a potential alternative to hormone replacement therapy in post-menopausal bone-loss prevention. Nevertheless, phytoestrogens can target other organs and may disrupt cell proliferation, or could modify endogenous steroid hormone metabolism. These mechanisms could be linked to an increased risk of developing cancer. We therefore studied the possible side effects of such treatments in an experimental model of menopause. Forty adult female Wistar rats were ovariectomized and fed with a genistein-, daidzein- or equol-supplemented diet at bone-sparing levels (10 mg/kg BW/day) for 3 months. The estrogenic effects were assessed by histological a…
Dietary xenoestrogens differentially impair 3T3-L1 preadipocyte differentiation and persistently affect leptin synthesis
International audience; Recent observations have highlighted adipogenesis alterations under exposure to several xenoestrogens at critical stages, and pointed at their possible involvement in the pathogenesis of obesity. However, it remains unclear whether these effects are mediated by classical estrogen receptor (ER) binding and subsequent transcriptional modulation. The aim of this study was to determine the (anti-)adipogenic impact of apigenin, bisphenol A, genistein and 17β-estradiol at the onset of adipose cell maturation, and to correlate it to their estrogenic potential. In steroid-free conditions, 3T3-L1 preadipocytes were induced to differentiate in the presence of xenoestrogens for…
Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin
The impact of early exposure to endocrine disruptor mixtures on mammary gland development is poorly known. Here, we identify the effects of a conception to weaning exposure of rats to the phytoestrogen genistein (G) and/or the antiandrogen vinclozolin (V) at 1 mg/kg-d, alone or in association. Using several approaches, we found that G- and GV-exposed rats displayed significantly greater epithelial branching and proliferation, wider terminal end buds than controls at PND35, as well as ductal hyperplasia and periductal fibrosis. Focal branching defects were present in V-exposed rats. An increased ER and AR expression was observed in G- and CV- as compared to V-exposed rats at PND35. Surprisin…
Actions différentielles de xéno-hormones alimentaires sur les organes reproducteurs, le foie et le tissu adipeux chez le rat femelle : aspects endocriniens, métaboliques et morphogénétiques en relation avec les processus de cancérogenèse
Differential actions of dietary xenohormones on the reproductive organs, the liver and the adipose tissue in the female rat : endocrine, metabolic and morphogenetic aspects regarding the carcinogenic process. Over the past décades, the incidence of hormone-dependent cancers has dramatically increased in Western countries as compared to Asian countries. Environmental and dietary compounds able to mimic and interfère with endogenous hormones, especially reproductive ones, may be involved and among these xenohormones. xenoestrogens (XE) are particularly pointed at. The objective of this thesis was to détermine the conséquences of chronic dietary exposure to phytoestrogens and chemical xenoestr…
Testing chemical carcinogenicity by using a transcriptomics HepaRG-based model?
The EU FP6 project carcinoGENOMICS explored the combination of toxicogenomics and in vitro cell culture models for identifying organotypical genotoxic- and non-genotoxic carcinogen- specific gene signatures. Here the performance of its gene classifier, derived from exposure of metabolically competent human HepaRG cells to prototypical non-carcinogens (10 compounds) and hepatocarcinogens (20 compounds), is reported. Analysis of the data at the gene and the pathway level by using independent biostatistical approaches showed a distinct separation of genotoxic from non-genotoxic hepatocarcinogens and non-carcinogens (up to 88 % correct prediction). The most characteristic pathway responding to …
Perturbateurs endocriniens : effet sur les préférences gustatives et l'obésité
International audience; Plusieurs études relient l’évolution de l’incidence de l’obésité à une évolution sociétale: l’accès des femmes au travail, les facilités de transport et l’essor de l’industrie agroalimentaire ont généré une "transition nutritionnelle" où le repas mijoté à base de produits frais a fait place au repas vite-prêt et fast-foods. La surconsommation de graisses et sucres et la moindre consommation de fruits et légumes sont bien souvent incriminés. Toutefois, l’usage concomitant de produits chimiques dans la production agricole et la confection de produits raffinés et/ou transformés, pourrait être un facteur aggravant, le taux d’obésité pouvant atteindre 50% en régions pollu…