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Environmental Factor

May 2011

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Extramural papers of the month

By Jerry Phelps
May 2011

SRP logo Research Brief

Beijing Olympics pollution controls could save lives

A study supported by the NIEHS Superfund Research Program found that the air pollution control measures put in place in Beijing during the 2008 Olympic Games would cut the lifetime risk of lung cancer almost in half. If the controls were continued, polycyclic aromatic hydrocarbon (PAH) pollution from combustion would drop dramatically and could translate to about 10,000 fewer lifetime cases of lung cancer.

The research found that in Beijing, a metropolitan area with 22 million people, the existing level of PAH pollution would lead to about 21,200 lifetime cases of lung cancer, but that would drop to 11,400 cases if pollution controls similar to those imposed during the 2008 Olympics were sustained.

China is now the leading emitter of PAH pollutants in the world. According to the study "PAH pollution was definitely reduced by the actions China took during the 2008 Olympics, such as restricting vehicle use, decreasing coal combustion, and closing some pollution-emitting factories."

Some, but not all, of the steps taken during the Olympics have been continued; however, the number of vehicles in Beijing, for instance, is continuing to increase 13 percent a year, the report noted. "Controlling vehicle emissions is key to reducing the inhalation cancer risks due to PAH exposure in Chinese megacities," the researchers wrote in their study.

Citation: Jia Y, Stone D, Wang W, Schrlau J, Tao S, Simonich SL. 2011. Estimated reduction in cancer risk due to PAH exposures if source control measures during the 2008 Beijing Olympics were sustained. Environ Health Perspect; doi:10.1289/ehp.1003100 [Online 8 Feb 2011].

Amyloid-binding compound extends lifespan in C. elegans

NIEHS-supported researchers report that a chemical dye that lights up amyloid protein clumps characteristic of Alzheimer's disease also slows aging in the nematode, C. elegans. The lifespan-boosting effects of the dye - called Thioflavin T (ThT) or Basic Yellow 1 - support the idea that the build-up of misshapen proteins is one of the fundamental events in the aging process. Drugs that stimulate the cell's natural repair and protein-recycling systems could be used to treat diseases of old age.

The study results show that small doses of Thioflavin T boosted the lifespan of roundworms by as much as 78 percent. Worms that did not receive the dye were all dead within 20 days, yet more than 80 percent of worms consuming a diet that included an optimum dose of ThT were still alive after the same period. ThT proved toxic at higher doses and shortened the worms' lives considerably.

The study authors suspect that ThT boosts lifespan by recognizing all kinds of toxic protein clumps. The dye reversed the effects of mutations that cause muscle proteins to misfold, and to become paralysed at a particular temperature. The team also found that worms that lack genes important to dealing with misshapen proteins do not live longer when fed Thioflavin T.

Citation: Alavez S, Vantipalli MC, Zucker DJ, Klang IM, Lithgow GJ. 2011( Exit NIEHS. Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature 472(7342):226-229.

Study finds no link between mercury exposure and cardiovascular disease

New research findings published by NIEHS grantees show no evidence that higher levels of mercury exposure are associated with higher risk for cardiovascular disease or stroke. Previous research has shown the beneficial cardiovascular effects of eating fish rich in omega-3 fatty acids, but other studies suggested that mercury exposure from fish consumption might be linked to higher risk of cardiovascular diseases. The current findings may allay those fears.

The researchers analyzed data from two studies, which included more than 170,000 men and women. Participants in both groups have answered questions every two years about their medical history, risk factors, disease incidence, and lifestyle. For the current analysis, the researchers measured mercury concentrations in stored toenail clippings in nearly 7,000 participants who did and did not experience a cardiovascular event during follow-up. Toenail mercury concentrations are an excellent biomarker of long-term mercury exposure. The researchers identified 3,427 new cases of coronary heart disease and stroke and matched them to 3,427 randomly chosen participants free of cardiovascular disease during follow-up.

After adjusting for age, gender, and other cardiovascular disease risk factors, the researchers found no association between mercury exposure and higher risk of cardiovascular disease. Trends toward lower risk with higher mercury levels were actually seen, which the researchers attribute to other beneficial effects of fish consumption.

Citation: Mozaffarian D, Shi P, Morris JS, Spiegelman D, Grandjean P, Siscovick DS, Willett WC, Rimm EB( Exit NIEHS. 2011. Mercury exposure and risk of cardiovascular disease in two U.S. cohorts. N Engl J Med 364(12):1116-1125.

Mitochondrial, but not nuclear ligase3 is required for cellular viability

A multi-institutional team of scientists including former NIEHS Principal Investigator Ben Van Houten, Ph.D., has determined that mitochondrial DNA ligase III (Lig3), an enzyme involved in various DNA repair pathways, is necessary for cellular growth and viability, while nuclear Lig3 is not required for cell survival. These findings were made through a series of exquisite experiments that incorporated various forms of the gene coding for Lig3 in mouse embryonic stem cells.

Previous research has demonstrated the importance of the nuclear complex Lig3 and its partner protein Xrcc1 in DNA single-strand break repair. The full characterization of Lig3 has been hampered by the fact that deletion of its gene is embryonically lethal in mice. In the current studies, the investigators introduced various forms of  Lig3 into mouse embryonic stem cells containing a conditional allele for Lig3 that could be deleted with Cre recombinase. This approach enabled them to determine that mitochondrial Lig3, but not nuclear, is necessary for cell viability. They also found that substitution of Lig1 for Lig3 in the mitochondria maintains cellular viability.

Citation: Simsek D, Furda A, Gao Y, Artus J, Brunet E, Hadjantonakis AK, Van Houten B, Shuman S, McKinnon PJ, Jasin M.( Exit NIEHS 2011. Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair. Nature 471(7337):245-248.

(Jerry Phelps is a program analyst in the NIEHS Division of Extramural Research and Training.)

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