UAB researchers examine BPA and breast cancer link (lower doses have higher effect)

[OKIsItJustMe]

https://www.uab.edu/news/briefs/item/1727-uab-researchers-examine-bpa-and-breast-cancer-link

Wednesday, October 12, 2011

UAB researchers examine BPA and breast cancer link

By Beena Thannickal

Chronic low-level exposure to a compound found in a variety of plastic household items could pose a threat to women who overproduce a protein linked with breast cancer, say researchers at http://www.uab.edu/">University of Alabama at Birmingham.

Coral Lamartiniere, Ph.D., professor in the http://medicine.uab.edu/pharmacology/">Department of Pharmacology and Toxicology and senior scientist in the http://www3.ccc.uab.edu/">UAB Comprehensive Cancer Center, and postdoctoral fellow Sarah Jenkins, Ph.D., assessed the effect of chronic, oral exposure to the compound bisphenol A (BPA) in mice genetically modified to overproduce the protein HER2/erbB2, present in about 15-30 percent of women with breast cancer. The results were published online Oct. 12, 2011, by the journal <http://ehp03.niehs.nih.gov/article/info:doi/10.1289/ehp.1103850|Environmental Health Perspectives>.

“We found the lower doses of BPA to be capable of activating several growth-factor-receptor pathways that previously have been implicated in cancer. This was not observed with the higher BPA doses,” Jenkins says. “This is counterintuitive since BPA in low levels was presumed to be safe.”

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(Moderators: Please note, US National Institutes of Health Open Publication, copyright concerns are nil.)
http://ehp03.niehs.nih.gov/article/info:doi/10.1289/ehp.1103850

Chronic Oral Exposure to Bisphenol A Results in a Non-Monotonic Dose Response in Mammary Carcinogenesis and Metastasis in MMTV-erbB2 Mice

Sarah Jenkins, Jun Wang, Isam Eltoum, Renee Desmond, Coral A. Lamartiniere

Abstract

Background: Bisphenol A (BPA) is a synthetic compound used to produce plastics and epoxy resins. Recent studies have found BPA to 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: This study investigated the role of chronic, oral exposure to BPA during adulthood on mammary carcinogenesis by using a transgenic mouse model which spontaneously develops tumors through over-expression of wildtype erbB2 (MMTV-erbB2).

Methods: MMTV-erbB2 mice were exposed to 0, 2.5, 25, 250, or 2500 µg BPA/L drinking water from 56 until 112 (mechanism of action) or 252 (tumorigenesis) days of age. 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 µg BPA/L, but not 2500 µg BPA/L, increased phosphorylation of erbB2, erbB3, IGF-1R, 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.

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[dixiegrrrrl]

1. "low but not high doses"...I find that interesting.