© 1998 by Oxford University Press
A cup of tea provides an antioxidant boost that may protect against several types of cancers, but so far the link has been reliably shown only in tea-sipping rodents and test tubes -- not in people. The antioxidants in green and black tea, called catechins, are "more potent than vitamins C and E" in their ability to scavenge potentially carcinogenic compounds called free radicals, said Catherine Rice-Evans, Ph.D., of the Antioxidant Research Centre in London.
However, Rice-Evans and other tea experts cautioned that despite promising early research, better animal models and more robust epidemiological studies are needed before tea research steams toward human trials. A decade may pass before enough clinical evidence accumulates to validate or refute tea's anti-cancer potential.
"The in vitro and animal data [are] very strong," said Jeffrey Blumberg, Ph.D., who researches tea antioxidants at Tufts University in Boston. "But clinical trials are the definitive approach."
Even without much clinical evidence, the 300 tea-swilling scientists and industry representatives who gathered at the Second International Symposium on Tea & Human Health, held in Washington in September, were steeped in news from a dozen promising studies.
Most of this research focused on the basic chemistry and biology of catechins. Among the results: Tea contains more antioxidants than do most fruits and vegetables; downing a single cup of green or black tea boosts total bloodstream antioxidant activity; and steeping tea for just 5 minutes releases 80% of its catechins.
Two studies showed catechins inhibit tumor growth in rats and mice, especially in lung-cancer-prone strains dosed with nicotine-derived carcinogens. A third rodent and dog project established catechins are not toxic, even at high doses.
Study Pitfalls
Despite all this promising work, some epidemiological data comparing tea drinkers and non-tea drinkers does not support the claim that tea prevents cancer. One study even found tea drinkers have higher cancer rates than non-tea drinkers; two others showed no tea effects. Difficulties sorting out possible confounding factors, such as other diet and health-related habits, may continue to hinder scientists searching for anti-cancer effects from tea, according to a spokesman from The Lipton Tea Co., Ltd., London.
Another pitfall -- not understanding the compounds under study -- derailed a 9-week, 24-subject, Lipton-sponsored study. While looking for tea's effects on colon cancer markers, Blumberg's team from Tufts did not take into account catechins' relatively speedy metabolism. Blumberg admitted that the team tested their subjects too infrequently, thus botching any chance of detecting tea's short-term effects. In defense of the null results, Blumberg added that finding modest protective effects, like those expected from tea, is tricky, even with large study populations.
A more promising early human study, this one from Beijing Dental Hospital, won robust applause from the tea-ed up audience as well as extensive media attention. The 6-month double-blind trial found 3 grams of tea (enough for about 2 cups) plus a topical tea extract reduces the size and proliferation of leukoplakia, precancerous oral plaque. Study leader Junshi Chen, M.D., said these results "provide some direct evidence of the protective effects of tea on cancer," but that larger, longer-term studies are needed.
-- Brian Vastag
For BRCA1, the noisiest problem has been where the BRCA1 protein is located in the cell. While most researchers have found the protein in the nucleus of normal cells, some have found evidence of the protein in the cytoplasm of malignant cells, and one group has reported that BRCA1 is present in the cell membrane and in the secretory apparatus. However, in a paper recently submitted to Nature Genetics, Cindy Wilson, Ph.D., from the Division of Hematology Oncology at the University of California, Los Angeles, appears to have settled whatever ambiguity remains.
"It's in the nucleus," said Wilson. "All the antibodies that are specific show distinctive nuclear dot patterns in cells." She compared 20 antibodies from several groups using many tests -- western blotting, immunoprecipitation, immunohistochemistry, and cytochemistry on individual cells. Because BRCA1 protein is expressed at very low levels in the nucleus, very clean antibodies are required to see it.
Besides cellular location, another clue to function comes from discovering the proteins that interact with BRCA1. To date, the list has grown quite large, including several enzymes (e.g., helicase, RNA polymerase, and ubiquitin hydrolase) as well as other proteins (e.g., Rad51, p53, BARD1, and CTIP). So far, no clear consensus has emerged about which proteins are important to BRCA1's function.
Adding to the murky picture, is the inability of researchers to produce mice lacking two copies of functional BRCA1 genes, so-called knock-out mice, which frequently provide insights into the function of the missing gene. Mouse embryos lacking BRCA1 protein do not survive.
Given these problems, a paper in the Aug. 14 Science was a first -- the first direct functional evidence for BRCA1. Researchers from the Department of Radiation Oncology, University of North Carolina at Chapel Hill, showed that cells deficient in BRCA1 were unable to repair DNA that was damaged by either ionizing radiation (gamma radiation) or hydrogen peroxide. The particular kind of repair that is defective in these cells is called transcription-coupled repair (TCR) -- involving machinery that tags along with RNA polymerase and repairs actively transcribing genes.
"Our results make sense with the data that show an association between BRCA1 and RNA polymerase," said Lori Gowen, a UNC graduate student and the paper's first author. "And it is consistent with BRCA1 being a tumor suppressor gene -- mutations will accumulate if the gene is involved in repair. But it still doesn't allow us to say whether BRCA1 is a part of the repair machinery or a transcription factor that regulates transcription of genes involved in TCR."
And that seems to be precisely the problem -- developing a good system for analyzing BRCA1, either in mice or in human cancer cells. The gene's enormous size suggests that the BRCA1 protein is likely to have several functions, probably involving DNA repair, transcriptional regulation of genes, or others.
Ralph Scully, M.D., Ph.D., a researcher in David Livingston's lab at the Dana-Farber Cancer Institute, Harvard Medical School, Boston, who discovered that BRCA1 associates with Rad51, believes the only way to make progress is to develop a good genetic system.
"We need a tractable genetic system to test out key hypotheses in the field. For example, we need to be able to add back normal BRCA1 to cells lacking functional BRCA1 and show that a specific defect can be reversed," he said.
-- Nancy J. Nelson
Tea Therapy? Out of the Cup, Into the Lab
Finding BRCA1's Function: A More Arduous Journey
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