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Extramural Papers of the Month

By Jerry Phelps
October 2009

Natural Food Products Can Treat Cancer

Combinations of natural food compounds and chemotherapy drugs provide promise as powerful and potentially less toxic chemotherapeutic treatment strategies, according to researchers at the Linus Pauling Institute. A recent study supported by NIEHS found that chlorophyllin, a derivative of chlorophyll, was 10 times more potent in killing colon cancer cells than the commonly used chemotherapeutic agent hydroxyurea.

The study, carried out in human colon cancer cell lines, found that chlorophyllin kills cancer cells by causing a disruption in cell division. The cells tend to be stalled in the S-phase of cell division when DNA replication occurs. The compound then induces apoptosis in a cytochrome c-independent manner resulting in cell death.

Chlorophyllin is inexpensive and has been proven in other NIEHS-funded research to be an effective treatment for aflatoxin-induced liver cancer. It can be ingested at relatively high levels without causing toxicity; however, it is poorly absorbed in the gut. Levels needed for therapeutic purposes as well as delivery systems are currently under study.

The researchers point out that other dietary cancer fighters also show promise. Organic forms of selenium have shown promise in targeting colon and prostate cancers.

Citation:Chimploy K, Díaz GD, Li Q, Carter O, Dashwood WM, Mathews CK, Williams DE,Bailey GS, Dashwood RH.(http://www.ncbi.nlm.nih.gov/pubmed/19585502?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) Exit NIEHS 2009. E2F4 and ribonucleotide reductase mediate S-phase arrest in colon cancer cells treated with chlorophyllin. Int J Cancer. 2009 May 11;125(9):2086-2094.

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Carbon Monoxide and Cardiovascular Disease in the Elderly

Low-dose exposure to the acutely poisonous gas carbon monoxide, even at levels far below national exposure limits, is associated with increased risk of adverse cardiovascular outcomes in elderly persons requiring hospitalization. This report comes from NIEHS grantee, Michelle Bell of Yale University, who is the recipient of an Outstanding New Environmental Scientist award from NIEHS.

The research team conducted an epidemiologic investigation of 126 urban communities across the U.S. The study results show that with each one part per million increase in the maximum daily one-hour exposure to carbon monoxide, the risk of hospitalization due to cardiovascular disease increases about one percent in people over age 65.

This evidence suggests that the currently accepted regulatory level of carbon monoxide may still be posing a health risk at least for this vulnerable population. The study indicates that as carbon monoxide levels rose, the risk of hospitalization increased. The findings were based on the analysis of hospital records for more than 9 million Medicare recipients matched to data on air pollution levels and weather from 1999 through 2005.

Although additional research is necessary to determine if the observed effect is due to exposure to carbon monoxide alone or in combination with other traffic-related pollutants, this study points toward a "positive and statistically significant association" between same-day carbon monoxide levels and increased risk for hospitalization for multiple cardiovascular diseases.

Citation: Bell ML, Peng RD, Dominici F, Samet JM. (http://www.ncbi.nlm.nih.gov/pubmed/19720933?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) Exit NIEHS 2009. Emergency hospital admissions for cardiovascular diseases and ambient levels of carbon monoxide: results for 126 United States urban counties, 1999-2005. Circulation 120(11):949-955. Epub ahead of print.

Story(http://www.niehs.nih.gov/news/newsletter/2009/october/science-sameday.cfm)

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Diesel Exhaust Linked to Cancer Development Through Blood Vessel Growth

NIEHS-supported scientists have identified a way that exposure to diesel exhaust stimulates the growth of cancerous tumors. Using a laboratory mouse research model, the research team determined that exposure to diesel exhaust particles stimulates the growth and formation of new blood vessels necessary for solid tumors to grow. The studies were carried out at exposure levels similar to those found in urban areas with heavy commuting traffic.

Most inhaled diesel exhaust particles are less than 0.1 micrometers in diameter, which enables them to penetrate the circulatory system and other organs and cause damage in just about any tissue in the body.

The researchers implanted small platforms embedded with normal endothelial cells, the cells that line blood vessels, under the skin of a group of healthy mice. In another set of mice, the researchers surgically created an ischemic condition in the hind limbs, resulting in a severe lack of oxygen.

Exposure to diesel exhaust for six hours per day caused a six-fold increase in new blood vessel formation in the ischemic limbs at eight weeks and a four-fold increase in the non-ischemic limbs compared to mice breathing normal air. Similar effects were seen in the mice with the implanted cells.

The team determined that exposure to diesel particles activates vascular endothelial growth factor, a chemical signal associated with new blood vessel development, and lowers activity for an enzyme involved in tumor suppression. The researchers are now conducting experiments to determine whether exposure to diesel exhaust influences metastasis of tumors as well.

Citation: Xu X, Kherada N, Hong X, Quan C, Zheng L, Wang A, Wold L, Lippmann M, Chen LC, Rajagopalan S, Sun Q. (http://www.ncbi.nlm.nih.gov/pubmed/19683567?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) Exit NIEHS 2009. Diesel exhaust exposure induces angiogenesis. Toxicol Lett. Epub ahead of print.

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Maternal Exposure to Air Pollution Lowers Children's IQ

Public health experts at Columbia University report that a mother's exposure to polycyclic aromatic hydrocarbons (PAHs) can lower her child's IQ. PAHs are widely found in urban air and result from the combustion of coal and automotive fuel. They are also found in tobacco smoke.

Non-smoking pregnant women of African-American or Dominican-American descent living in the South Bronx and Harlem were enrolled in the study. They wore personal air monitors during pregnancy and provided additional information about their work and home environments. The women were split into high- and low-exposure groups based on whether their PAH exposure was above or below the median of 2.26 nanograms per cubic meter of air. Their children were monitored from the perinatal period until age five when they were given a standard intelligence exam. On average, the IQ scores of children in the high exposure group were about four points lower than children in the low exposure group.

An IQ deficit in the range of four points is believed to affect how well children perform in school and how well they score on standardized tests. These deficits are similar to those seen in children with significant lead exposure.

Citation: Perera FP, Li Z, Whyatt R, Hoepner L, Wang S, Camann D, Rauh V. (http://www.ncbi.nlm.nih.gov/pubmed/19620194?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) Exit NIEHS 2009. Prenatal airborne polycyclic aromatic hydrocarbon exposure and child IQ at age 5 years. Pediatrics. 124(2):e195-202. Epub ahead of print.

Story(http://www.niehs.nih.gov/news/newsletter/2009/august/science-childs-iq.cfm)

(Jerry Phelps is a program analyst in the NIEHS Division of Extramural Research and Training. Each month, he contributes summaries of extramural papers to the Environmental Factor.)



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