Environmental Factor, July 2005, National Institute of Environmental Health Sciences
DERT Papers of the Month - May 2005
By Jerry Phelps
1) Timms BG, Howdeshell KL, Barton L, Bradley S, Richter CA, Vom Saal FS. Estrogenic chemicals in plastic and oral contraceptives disrupt development of the fetal mouse prostate and urethra. Proc Natl Acad Sci U S A. 2005 May 10;102(19):7014-9.
Implications: Since both bisphenol A and ethinylestradiol are known to cross the placenta and enter the fetus, these results may have direct implications on human health. The dose of ethinylestradiol used in the experiment was actually lower than that of women taking oral contraception. The bisphenol A dose used produced fetal levels lower than those seen in human fetuses at birth. Therefore, this experiment is highly relevant to everyday human exposures. The study authors conclude that these effects "warrant a thorough reevaluation of risks posed by doses of both ethinylestradiol and bisphenol A below those to which human fetuses are exposed."
2) Que LG, Liu L, Yan Y, Whitehead GS, Gavett SH, Schwartz DA, Stamler JS. Protection from experimental asthma by an endogenous bronchodilator. Science. 2005 Jun 10;308(5728):1618-21. Epub 2005 May 26.
Implications: This study shows that GSNO reductase is very important in the regulation of the size of the airway under normal conditions and in response to allergen challenge. Furthermore, a deficiency of SNOs may make fundamental contributions to the development of asthma. Team leader Jonathan Stamler reports that the findings "suggest that the SNO deficit seen in patients with asthma may result from increased GSNO reductase activity" and that "the enzyme may therefore offer a novel target for therapies designed to alleviate airway obstruction." In addition, GSNO repletion in patients may treat asthmatic symptoms.
3) Munoz-de-Toro M, Markey C, Wadia PR, Luque EH, Rubin BS, Sonnenschein C, Soto AM. Perinatal exposure to Bisphenol A alters peripubertal mammary gland development in mice. Endocrinology. 2005 May 26; [Epub ahead of print]
Implications: The bisphenol A-induced increases in terminal end bud density at puberty as well as the increased numbers of ducts reported previously by this laboratory in adult animals are most troubling, since these two structures are the sites where cancer arises in humans and rodents. These findings suggest that bisphenol A exposure in humans may be an important risk factor for breast cancer and should be studied more intensely.
4) Members of the Toxicogenomics Research Consortium. Standardizing global gene expression analysis between laboratories and across platforms. Nat Methods. 2005 May;2(5):351-6.
Implications: The results from these studies indicate that microarray experiments can be comparable across multiple laboratories, especially when a common platform and set of procedures are used. These advances in microarray technology demonstrate to the scientific community how to obtain more consistent and reliable results. Standardizing microarray techniques can accelerate the pace of scientific discovery about biological responses to environmental stressors. Ultimately this could improve our ability to detect very early indicators of diseases like cancer to identify people at risk for environmentally related diseases.