PMID- 21988766
OWN - NLM
STAT- MEDLINE
DCOM- 20120306
LR  - 20211020
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 119
IP  - 11
DP  - 2011 Nov
TI  - Chronic oral exposure to bisphenol A results in a nonmonotonic dose response in 
      mammary carcinogenesis and metastasis in MMTV-erbB2 mice.
PG  - 1604-9
LID - 10.1289/ehp.1103850 [doi]
AB  - BACKGROUND: Bisphenol A (BPA) is a synthetic compound used to produce plastics 
      and epoxy resins. BPA can leach from these products in appreciable amounts, 
      resulting in nearly ubiquitous daily exposure to humans. Whether BPA is harmful 
      to humans, especially when administered orally in concentrations relevant to 
      humans, is a topic of debate. OBJECTIVES: In this study, we investigated the role 
      of chronic oral exposure to BPA during adulthood on mammary carcinogenesis by 
      using a transgenic mouse model that spontaneously develops tumors through 
      overexpression of wild-type erbB2 [mouse mammary tumor virus (MMTV)-erbB2]. 
      METHODS: MMTV-erbB2 mice were exposed to 0, 2.5, 25, 250, or 2,500 microg BPA/L 
      drinking water from 56 until 112 days of age (for mechanism of action) or 252 
      days of age (for tumorigenesis). Cellular and molecular mechanisms of BPA action 
      in the mammary gland were investigated via immunohistochemistry and 
      immunoblotting. RESULTS: Only low doses of BPA significantly decreased tumor 
      latency and increased tumor multiplicity, tumor burden, and the incidence of 
      metastasis. All BPA doses significantly increased the cell proliferation index, 
      but only the higher doses also increased the apoptotic index in the mammary 
      gland. At the molecular level, 25 microg BPA/L, but not 2,500 microg BPA/L, increased 
      phosphorylation of erbB2, erbB3, insulin-like growth factor 1 receptor, and Akt 
      in the mammary gland. DISCUSSION: Low, but not high, BPA doses significantly 
      accelerated mammary tumorigenesis and metastasis in MMTV-erbB2 mice. The combined 
      ratio of cell proliferation and apoptosis indices and alterations in protein 
      expression best predicted the ability of each dose of BPA to alter tumorigenesis 
      in this model.
FAU - Jenkins, Sarah
AU  - Jenkins S
AD  - Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 
      Birmingham, Alabama, USA.
FAU - Wang, Jun
AU  - Wang J
FAU - Eltoum, Isam
AU  - Eltoum I
FAU - Desmond, Renee
AU  - Desmond R
FAU - Lamartiniere, Coral A
AU  - Lamartiniere CA
LA  - eng
GR  - U01 ES012771/ES/NIEHS NIH HHS/United States
GR  - R25 CA07888-22/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20111012
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Carcinogens, Environmental)
RN  - 0 (Phenols)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - MLT3645I99 (bisphenol A)
SB  - IM
MH  - Animals
MH  - Benzhydryl Compounds
MH  - Carcinogens, Environmental/administration & dosage/*toxicity
MH  - Cell Transformation, Neoplastic/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Mammary Glands, Animal/drug effects/*metabolism
MH  - Mammary Neoplasms, Animal/*chemically induced/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - *Neoplasm Metastasis
MH  - Phenols/administration & dosage/*toxicity
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptor, IGF Type 1/metabolism
MH  - Time Factors
PMC - PMC3226508
COIS- The authors declare they have no actual or potential competing financial 
      interests.
EDAT- 2011/10/13 06:00
MHDA- 2012/03/07 06:00
PMCR- 2011/11/01
CRDT- 2011/10/13 06:00
PHST- 2011/04/22 00:00 [received]
PHST- 2011/07/29 00:00 [accepted]
PHST- 2011/10/13 06:00 [entrez]
PHST- 2011/10/13 06:00 [pubmed]
PHST- 2012/03/07 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - ehp.1103850 [pii]
AID - 10.1289/ehp.1103850 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2011 Nov;119(11):1604-9. doi: 10.1289/ehp.1103850. Epub 
      2011 Oct 12.