Epidemiologic studies indicate that high serum levels of chlorinated pollutants such as dioxins or pesticides constitute a risk factor for breast cancer in postmenopausal women. This finding has been attributed to the ability of organochlorine compounds to induce the expression of cytochrome
P450 (CYP) enzymes, which are thought to increase the burden of genotoxic metabolites. However, it was not clear whether the incriminated pollutants accumulate to sufficiently high levels within the human body to be able to promote significant transcriptional responses. Here, milk samples
from nursing mothers were processed by gel permeation chromatography to isolate complex mixtures of residues containing both endogenous hormones and lipophilic contaminants of environmental origin. High-density oligonucleotide microarrays were used to monitor global transcriptional profiles
in a human cell line (MCF7) that represents one of the most frequently used model systems to study breast cancer biology. We found that all breast milk extracts were able to reprogram the genome of MCF7 cells by imposing a typically estrogenic expression fingerprint. This estrogenic background
was overlapped only by the induction of transcripts coding for CYP1A1 and, to a minor degree, CYP1B1. The magnitude of induction of these metabolic enzymes correlated with the respective organochlorine concentrations. Thus, in support of previous epidemiologic studies, we demonstrate
that contaminants released from human adipose tissue trigger a potentially genotoxic pathway in cells from the mammary gland.
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Document Type: Research Article
May 1, 2008
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International Journal for Chemistry and Official Membership Journal of the Swiss Chemical Society (SCS) and its Divisions
CHIMIA, a scientific journal for chemistry in the broadest sense, is published 10 times a year and covers the interests of a wide and diverse readership. Contributions from all fields of chemistry and related areas are considered for publication in the form of Review Articles and Notes. A characteristic feature of CHIMIA are the thematic issues, each devoted to an area of great current significance.
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