Dietary exposure in utero and during lactation to a mixture of genistein and an anti-androgen fungicide in a rat mammary carcinogenesis model

Reprod Toxicol. 2015 Jul:54:101-9. doi: 10.1016/j.reprotox.2014.05.016. Epub 2014 Jun 8.

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.

Keywords: Anti-androgen; Endocrine disruption; Gestational and lactational exposure; Mammary gland carcinogenesis; Phytoestrogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Age Factors
  • Androgen Antagonists / toxicity*
  • Animals
  • Breast Neoplasms / chemically induced*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control
  • Carcinoma in Situ / chemically induced*
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma in Situ / prevention & control
  • Cell Proliferation / drug effects
  • Diet
  • Disease Models, Animal
  • Endocrine Disruptors / toxicity*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Fungicides, Industrial / toxicity*
  • Genistein / toxicity*
  • Gestational Age
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / 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

Substances

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