Dr. Roderick Dashwood, Linus Pauling Institute
Q: Much of your research is focused on tea and cancer. How did you get interested in tea?
A: A study by my former professor from England, Costas Ioannides, reported that when rats were given two percent green tea in their drinking water, the tea produced changes in their liver enzymes. What really grabbed my attention was that the liver enzyme most strongly altered in those studies was the same enzyme that metabolically activates heterocyclic amines. We've been working with these compounds from cooked meat and cooked fish and know a lot about their chemistry and mutagenicity. One of the important liver enzymes that converts these compounds from an inactive form to their active form is called CYP1A2, which is part of the cytochrome P450 system. That specific isozyme was strongly induced by green tea, suggesting the possibility that tea might activate rather than detoxify these cooked-meat mutagens. We therefore hypothesized that rats fed green tea and given heterocyclic amines might actually be at an increased risk for colon cancer. When we did the experiment, we found that rather than increasing the risk, green tea decreased the risk of developing precancerous lesions in the colon called aberrant crypt foci.
Q: Are these liver enzymes the same in rats and humans?
A: The classification of these cytochrome P450 enzymes in rats and humans is a little tricky and complicated. While the terminology is often the same, actual enzyme activity can vary in the different species. We do know, however, that green tea induced the detoxification of the cooked-meat mutagens, resulting in fewer preneoplastic lesions. We also know that the detoxified metabolites in rats, called glucuronides, are also the primary metabolites that are excreted in people who eat meat. Again, there are some slight differences in chemical structure between the rat and human metabolites, but they are formed by similar metabolic processes.
Q: Based on those results, do you think that tea would likely protect against colon and other cancers in people?
A: I don't really know. There is excellent evidence for the chemoprotective role of tea against various cancers in animals, but the human epidemiological evidence is less compelling.
Q: How are the cooked-meat mutagens formed in food?
A: During high-temperature cooking, amino acids like L-phenylalanine fuse with creatine or creatinine, which is present in muscle meat. This process may be influenced by the presence of certain types of sugars, as well. Cooking pyrrolyzes these compounds to create new mutagens. They were identified as potent bacterial mutagens in the 1970s by Sugimura and colleagues in Japan, although they were probably first discovered about 60 years ago by a Swedish scientist who was looking at extracts of grilled horsemeat injected into mice that produced tumors.
Q: What kind of teas do you use in your experiments?
A: In our initial studies we found that green tea was more effective than black tea at inhibiting the aberrant crypt foci induced by cooked-meat mutagens. Subsequently, our lab has investigated white tea.
Q: How does white tea differ from the other types of tea?
A: Typically, the tea leaf is picked and withered, followed by a number of other processing steps that oxidize the polyphenols. That's true for green tea, oolong tea, and black tea. With white tea, there is no withering step or further processing. Also, white teas contain buds and leaves, whereas other teas are mainly leaves, so the dried tea doesn't look green--it has a pale appearance. This was nicely illustrated in the LPI Fall/Winter 2002 Newsletter article by Jane Higdon.
Q: You mentioned polyphenols. Have you found that these compounds extracted and purified from tea are as effective as whole tea?
A: That is one of the interesting studies that we did early on. We decided to compare white tea with green tea and found that the white teas had greater antimutagenic activity in our assays than the green teas. Then we analyzed white teas using high-performance liquid chromatography. We wanted to know if the greater antimutagenic activity was due to some unique polyphenol in the white tea. While all of the major constituents that we saw in green tea were also present in the white tea, the relative levels were different. After we identified the nine major catechins and caffeine that were in the teas, we made an artificial tea containing those compounds in the same concentrations found in tea. When we tested the reconstituted tea, it had only about 50% of the antimutagenic potency of the complete tea. This tells us that while...