Chlorophyll, the natural plant pigment that lends its color to grass, leaves, and many of the vegetables we eat, may play an important role in prevention of certain cancers. Researchers in the early 1980s discovered that chlorophylls and related chemicals can inhibit the ability of certain DNA-damaging chemicals to cause mutations in bacteria. How might this kind of "anti-mutagenic" activity be important in cancer prevention? Molecular geneticists now know that most if not all human cancers carry mutations in one or more genes that control the rates at which individual cells divide, differentiate, or die. According to current thinking, various combinations of mutations that upset this delicate balance to favor uncontrolled cell growth can then enable this irreversibly damaged cell to form a primary cancer in the lung, liver, blood, bone, skin, or another body organ. Therefore, it seems at least theoretically possible that the anti-mutagenic power of the chlorophylls might allow them to inhibit or reduce the formation of cancers in humans. Recent progress in our laboratory and elsewhere has brought this promise closer to realization.
|Much of that pioneering work was carried out at Oregon State University by Professor Russel Sinnhuber who immediately recognized the promise of the rainbow trout as a model of exquisite sensitivity for the study of liver cancer. Postdoctoral fellows and graduate students in my laboratory have been using this model for the past 12 years in a search for means to reduce AFB1-based liver cancer risk.|
| Dr. Roderick
Dashwood, a postdoctoral associate who came to my lab in 1986, became interested
in chlorophylls. Although their anti-mutagenic activity in bacterial assays
was then well known, no one knew if chlorophylls could have a protective
effect in animals. Rod discovered that rainbow trout fed AFB1
together with chlorophyllin, a simple water-soluble chlorophyll derivative,
had greatly reduced damage to their liver DNA compared to trout receiving
AFB1 alone. Would this reduce liver cancer development?
That question was answered by a Ph.D. student, Vibeke Breinholt, who showed
that even very modest dietary levels of chlorophyllin, roughly equivalent
to the chlorophyll in one small helping of spinach, strongly reduced liver
cancer in trout co-fed AFB1. Vibeke's results also
showed clearly that this reduction could be directly attributed to reduced
AFB1-DNA damage in the liver. These very exciting findings
were the first ever to reveal a true cancer-protective effect by chlorophylls.
Several important questions now remained before these findings might be taken to human trials: Was the effect unique to trout or would chlorophyllin inhibit cancer in other animals? How did the cancer inhibition come about and would this mechanism likely apply to AFB1-exposed humans? Could chlorophyllin inhibit cancers other than liver or caused by carcinogens other than AFB1 -- that is, might it have a potentially broader applicability? Would native chlorophylls in the plants we eat be as effective as the chlorophyllin derivative? The answers to most of these questions are now known. Rod Dashwood, presently at University of Hawaii, found that chlorophyllin in the drinking water could strongly reduce colon cancer development in rats exposed to heterocyclic amines, which are potent carcinogens isolated from meats broiled at high temperature. Others found similar protection against skin tumors in mice painted with polyaromatic hydrocarbons, and we have shown protection against stomach and liver cancer in trout treated with a carcinogenic hydrocarbon found in tobacco smoke. Subsequent work by Vibeke, Michael Schimerlik, and Tetsu Hayashi showed that chlorophyllin associated tightly with AFB1, even in the acidic environment of the stomach and at the temperature of the human body, which most likely explained the ability of chlorophyllin to greatly reduce bioavailability or uptake of AFB1 from the diet. John Groopman and Tom Kensler two colleagues at Johns Hopkins University, found that dietary chlorophyllin was as effective at preventing AFB1-DNA damage in the liver of rats as it was in trout. Such a simple and safe protective mechanism was almost sure to apply to humans!
|Based on these findings and the known safety of chlorophyllin, the National Institute of Environmental Health Sciences recently funded a research grant for Drs. Kensler, Groopman, and me to conduct a chlorophyllin intervention trial in a region of China where people are unavoidably exposed to high levels of AFB1 in their diet. In August I ventured to the little town of Daxin where Tom and I, with the help of local physicians from the Qidong Liver Cancer Institute, initiated the trial.||
Typical village scene
in Daxin, China
| After screening
500 volunteers, over 200 people were identified with high levels of chronic
AFB1 exposure. Of these, 90 people will receive a green
sugar pill and 90 will receive a green chlorophyllin tablet with each meal
for four months. (The samples are all coded and nobody knows who gets what
until the code is revealed at the very end). Blood and urine samples are
being collected every second week. By analysis of these samples we hope
to tell if chlorophyllin alters AFB1 uptake and liver
DNA damage in people as it does in trout and rats. The experiment can detect
a reduction of 20% or greater, and, of course, this is what we hope to see.
On a personal note, those of us trained in the basic sciences rarely have
an opportunity to see our work applied directly to the reduction of human
disease and misery. It would be rewarding indeed to see the trout model
applied full circle from the discovery of a major form of human cancer risk,
to the discovery of a simple means for its prevention. By this time next
year I hope to be able to tell you how this turns out.
Our excitement must also be tempered with the realism that chlorophylls will not be the magic bullet against all cancer. First and foremost, there is no evidence that chlorophylls can cure cancer once it is started; we saw no such activity in trout. Nor is it likely that chlorophylls will be effective for prevention of all cancers. With the exception of a few substances and chemicals like tobacco smoke and AFB1, we do not know what causes most human cancers, nor is cancer simply equated with mutagenesis. For example, some chemicals, such as dioxin and PCBs, appear to cause cancer in rats by upsetting patterns of gene regulation and hormonal response without any ability to damage DNA directly. Still other chemical carcinogens that do damage DNA lack the appropriate structure to interact with the chlorophylls. Route of exposure is also an important consideration. Inhaled tobacco smoke and sunlight are the two major mutagenic carcinogens to which people in the United States are exposed. However, neither of these carcinogens reaches its target organ through the digestive tract and, since chlorophylls are only poorly absorbed into the body, it seems highly unlikely that dietary chlorophylls could be effective against skin cancer in sun bathers or lung cancer in smokers. Chlorophylls are equally unlikely to be effective against virus-associated cancers, such as those of the cervix and viral leukemia. Still, chlorophyllin has not been tested in these situations, and science often throws us big surprises.
The above reservations notwithstanding, there is a solid scientific basis to hope that chlorophyllin will protect against AFB1-based liver cancer. Short-term trials may also soon be conducted to assess protection in humans against the heterocyclic amines, which many researchers view as a risk factor for colon cancer for people consuming a typical Western diet. We do not yet know if natural chlorophylls will be effective, but these experiments are now in progress in our laboratory. Meanwhile, these studies provide additional reasons to keep your intake of dark green vegetables high. For more information on chlorophyll and chlorophyllin, see the Linus Pauling Institute's Micronutrient Information Center.
Last updated November, 1997
Honoring a Scientific Giant with Research Toward Longer, Better Lives