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DERT Papers of the Month - June 2005

By Jerry Phelps
August 2005

1) Cook JD, Davis BJ, Cai SL, Barrett JC, Conti CJ, Walker CL. Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8644-9; and Walker CL, Stewart EA. Uterine fibroids: the elephant in the room. Science. 2005 Jun 10;308(5728):1589-92. Review.

Implications: Results from these findings indicate that reprogramming of genes during the developmental period as a consequence of an early life exposure to an artificial estrogen can interact with a preexisting genetic condition to increase tumor formation and the severity of the disease. This study differs from traditional carcinogenicity studies that have shown that environmental exposures lead to genetic mutations that are part of multiple events leading to carcinogenesis. If additional research confirms these results, this study's findings could have implications for other hormonally-mediated cancers such as those of the breast and prostate.

2) O'Neill MS, Veves A, Zanobetti A, Sarnat JA, Gold DR, Economides PA, Horton ES, Schwartz J. Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function. Circulation. 2005 Jun 7;111(22):2913-20.

Implications: These findings indicate that diabetics may be at higher risk for adverse cardiovascular events during periods of high particulate matter air pollution. In an accompanying editorial, Rajagopalan and colleagues suggest that particulates may have adverse effects by causing abnormalities in the generation of nitric oxide, a gas which relaxes smooth muscle cells found in the heart and arteries, enabling easier blood flow. Further research is necessary to confirm these results and to determine why diabetics are particularly sensitive. In addition to following their health care provider's recommendations on diet, exercise, and medications, diabetics should minimize outdoor physical activity on days with high particulate matter pollution.

3) Rieder MJ, Reiner AP, Gage BF, Nickerson DA, Eby CS, McLeod HL, Blough DK, Thummel KE, Veenstra DL, Rettie AE. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med. 2005 Jun 2;352(22):2285-93.

Implications: These results suggest that individual genetic make-up could be a big factor in a person's response to warfarin and therefore the correct dose. Racial differences also seem to be important in that Asian Americans generally had the low-dose genotype while African-Americans had the high-dose genotype. People of European descent generally fell in the middle. The authors conclude that genetic analysis of VKORC1 "should be an essential component of prospective studies aimed at investigating the value of genotyping for warfarin therapy."

4) Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 2005 Jun 24;308(5730):1909-11.

Implications: These results support the theory that free radical and reactive oxygen molecules generated in the mitochondria are very important in aging processes. It is too early to say that human lives could be extended by the administration of antioxidant compounds; however, this study has produced exciting results with implications for longevity, possible new treatments for aging related illnesses, and healthier aging.



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