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: P Phrakonkham, J P Brouland, H El Sheikh Saad, R Bergès, C Pimpie, M Pocard, M C Canivenc-Lavier, M Perrot-Applanat
• Journal: Reproductive toxicology (Elmsford, N.Y.) (Reprod Toxicol) Vol. 54 Pg. 101-9 (Jul 2015) ISSN: 1873-1708 [Electronic] United States
• PMID: 24915137 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Androgen Antagonists
• Endocrine Disruptors
• Fungicides, Industrial
• Oxazoles
• Receptors, Estrogen
• Receptors, Progesterone
• 9,10-Dimethyl-1,2-benzanthracene
• Genistein
• vinclozolin

Topics

• 9,10-Dimethyl-1,2-benzanthracene
• Age Factors
• Androgen Antagonists (toxicity)
• Animals
• Breast Neoplasms (chemically induced, metabolism, pathology, prevention & control)
• Carcinoma in Situ (chemically induced, metabolism, pathology, prevention & control)
• Cell Proliferation (drug effects)
• Diet
• Disease Models, Animal
• Endocrine Disruptors (toxicity)
• Epithelial Cells (drug effects, metabolism, pathology)
• Female
• Fungicides, Industrial (toxicity)
• Genistein (toxicity)
• Gestational Age
• Mammary Glands, Animal (drug effects, metabolism, pathology)
• Maternal Exposure (adverse effects)
• Oxazoles (toxicity)
• Pregnancy
• Prenatal Education
• Rats, Wistar
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Risk Assessment
• Risk Factors
• Tumor Burden (drug effects)