title: Dietary exposure in utero and during lactation to a mixture of genistein and an anti-androgen fungicide in a rat mammary carcinogenesis model.
abstract: 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 latency. G exposure decreased number of tumors, incidence and multiplicity. Unexpectedly, GV exposure increased tumor volume (p=0.04 vs controls) and epithelial proliferation (p=0.001 vs controls; p=0.005 vs G,V only). All tumors were in situ carcinomas. Concluding, maternal gestation/lactation exposure to a vinclozolin and genistein mixture significantly increases offspring tumor growth without changes in carcinogenesis susceptibility.
authors.affiliation: INRA UMR1324, Centre des Sciences du Gout et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Dijon, France.
authors.forename: P
authors.initials: P
authors.lastname: Phrakonkham
authors.affiliation: INSERM U965, Hôpital Lariboisière, F-75475 Paris, France; Université Paris 7, F-75475 Paris, France; Service d'Anatomopathologie, Hôpital Lariboisière, F-75475 Paris, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Brouland
authors.affiliation: INSERM U965, Hôpital Lariboisière, F-75475 Paris, France; Université Paris 7, F-75475 Paris, France.
authors.forename: H El Sheikh
authors.initials: Hel S
authors.lastname: Saad
authors.affiliation: INRA UMR1324, Centre des Sciences du Gout et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Dijon, France.
authors.forename: R
authors.initials: R
authors.lastname: Bergès
authors.affiliation: INSERM U965, Hôpital Lariboisière, F-75475 Paris, France; Université Paris 7, F-75475 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Pimpie
authors.affiliation: INSERM U965, Hôpital Lariboisière, F-75475 Paris, France; Université Paris 7, F-75475 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Pocard
authors.affiliation: INRA UMR1324, Centre des Sciences du Gout et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Dijon, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Canivenc-Lavier
authors.affiliation: INSERM U965, Hôpital Lariboisière, F-75475 Paris, France; Université Paris 7, F-75475 Paris, France. Electronic address: martine.applanat@inserm.fr.
authors.forename: M
authors.initials: M
authors.lastname: Perrot-Applanat
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000367:Age Factors; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D002278:Carcinoma in Situ / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D049109:Cell Proliferation / Q000187:drug effects; D004032:Diet; D004195:Disease Models, Animal; D052244:Endocrine Disruptors / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D019833:Genistein / Q000633:toxicity*; D005865:Gestational Age; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018811:Maternal Exposure / Q000009:adverse effects*; D010080:Oxazoles / Q000633:toxicity*; D011247:Pregnancy; D064186:Prenatal Education; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D005659:Fungicides, Industrial; D010080:Oxazoles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015127:9,10-Dimethyl-1,2-benzanthracene; D019833:Genistein; C025643:vinclozolin
keywords: Anti-androgen; Endocrine disruption; Gestational and lactational exposure; Mammary gland carcinogenesis; Phytoestrogen