Research Notes

Epidemiologists often investigate connections between cancers and chemicals in the environment. But molecular biologists now are starting to describe the molecular mechanisms for how such compounds might promote cancerous growth. A recent study is among the first to show how carcinogens trigger cancer-causing genetic events (A. Bardelli et al., "Carcinogen-specific induction of genetic instability," Proceedings of the National Academy of Sciences, Early Edition, April 10, 2001, www.pnas.org/cgi/

Apr 30, 2001
Eugene Russo
Epidemiologists often investigate connections between cancers and chemicals in the environment. But molecular biologists now are starting to describe the molecular mechanisms for how such compounds might promote cancerous growth. A recent study is among the first to show how carcinogens trigger cancer-causing genetic events (A. Bardelli et al., "Carcinogen-specific induction of genetic instability," Proceedings of the National Academy of Sciences, Early Edition, April 10, 2001, <www.pnas.org/cgi/content/abstract/081082898v1). Johns Hopkins University cancer researchers treated genetically stable human cells with two carcinogens found in food: PhiP (2-amino-1-methyl-6-phenylimidazo [4,5-b] pyrdine) and MNNG (methylating agent methyl-N'-nitrosoguanine). PhiP is found typically in well-cooked beef and chicken; MNNG is produced in the colon during food metabolism. The researchers found that only cells that had acquired a mutation in a mismatch repair gene survived MNNG exposure, but the survivors were not able to efficiently repair DNA replication mistakes--a defect that can lead to cancer. Cells that survived PhiP exposure had abnormal numbers of chromosomes, which also can lead to cancer. According to senior author Christoph Lengauer, an assistant professor of oncology at Johns Hopkins, the only previous research illustrating the molecular mechanism of carcinogens were studies linking cigarette ingredients to mutations in the DNA of cancer cells. "We have known for a long time that carcinogens, especially in the environment [and in] nutrition, cause direct damage to genes," he says. "What our findings sort of indicate is that environmental factors shape the entire genetic evolution of cancer cells." Lengauer suggests that research like his group's might one day be used to optimize chemotherapy treatments by genetically profiling a cancer patient and identifying the most appropriate therapeutic reagents for each individual.

Monitoring West Nile Virus

Since West Nile virus invaded New York City two summers ago, this mosquito-borne, arborvirus disease has spread, reaching up into New Hampshire and Vermont and down through North Carolina. Anticipating that the disease will travel further this summer, the Centers for Disease Control and Prevention (CDC) is recommending that all hospitalized patients having encephalitis of unknown etiology in the contiguous 48 states be screened for West Nile by testing the cerebrospinal fluid, and appropriately timed acute and convalescent serum specimens for IgM ELISA antibody. Up until now, such surveillance had been limited to New York, New Jersey, and Connecticut, where the virus sickened numerous people and killed two last year. "It's an exotic virus; it's spreading, and we see no reason that it's not going to continue its spread," says Robert Nasci, a research entomologist in the CDC's division of vector-borne infectious diseases. "We need to continue to monitor its spread through the [United States], to see what public health risks it will impose as it gets into new habitats." Nasci notes that such surveillance, called enhanced passive surveillance (EPS) relies on physician education programs to reach infectious diseases professionals and neurologists with the proper case definition. State public health departments will distribute this information, which will include symptom descriptions and details on getting blood samples to a lab for appropriate testing. By the end of the 2000 transmission season, West Nile had been identified in 12 states, according to a CDC report. There were 21 people, 63 horses, 4,304 birds--78 species in all--and 14 species of mosquitoes affected.