Environ Health Perspect 102-5, 1994: Forum

Eat Cabbage to Fight Cancer

Vegetable vaccine? Substances in cabbage and other vegetables may be strong protection against cancer.

At the Chapel Hill campus of the University of North Carolina, 10 people will soon be eating a pound a day of a mixture of cabbage, brussel sprouts, and cauliflower. A running analysis of how active substances in these vegetables break down in peoples bodies and, more importantly, what cellular mechanisms they affect, may shed further light on the value these vegetables have in preventing certain human cancers.

Cabbage and its cousins may strongly protect against cancers of the digestive system, such as the tongue, lip, oral cavity, esophagus, and colon, according to researcher Lenore Kohlmeier, a professor of nutrition and epidemiology at the UNC School of Public Health and Medicine. Surprisingly, these vegetables may also protect against breast cancer, she said.

Kohlmeier uncovered evidence of cabbage's anticancer effects when she looked at variations in nutritionally based cancer rates across Europe. She picked the newly unified Germany as a test country because differences in nutrition still existed between the formerly socialist East Germany and the wealthier, democratic West Germany. Kohlmeier expected that because nutrition was better in the west, residents there would have fewer related cancers.

But Kohlmeier found just the opposite. Residents of East Germany had significantly fewer cancers of the gastrointestinal tract than West Germans, although stomach cancer was higher in the east--possibly due to less refrigeration, according to Kohlmeier. Easterners also had a much lower incidence of breast cancer.

"I was very surprised. It just didn't make sense," she said. "Despite the fact that easterners ate more fat and fewer fresh fruits and vegetables and were overweight, they had significantly fewer nutritionally related cancers."

Digging further, Kohlmeier discovered "an amazing 40-fold difference" in cabbage consumption across Europe (as exemplified in the two Germanys) because there is more cabbage in the east and because it doesn't need to be kept refrigerated. "I have usually only seen a fourfold difference in other vegetables," she says. She also found epidemiological evidence that the protective effect of cabbage on cancer dissipates over time.

Kohlmeier's laboratory study of cabbage consumption aims to define just what substances in the cruciferous family may be anticancer agents. Her research joins just a handful of other studies, mostly done in animals, that are trying to link diet and cellular mechanisms that promote or protect against cancer. What is known is that compounds called glucosinolates, which give cruciferous vegetables their taste, are broken down during metabolism by enzymes in the plants known as myrosinases. The by-products are very active, short-lived substances called isothiocyanates.

"Isothiocyanates may help to disarm carcinogens by getting them out of their toxic state and out of the body," says Kohlmeier. Detoxification occurs mainly in the liver and enhances excretion of the carcinogens. The importance of one of these cruciferous compounds, sulforaphane, as an inducer of enzymes that detoxify carcinogens was highlighted in a report in the March 1992 issue of Proceedings of the National Academy of Science, by researchers at the Johns Hopkins University School of Medicine.

Other mechanisms resulting from these foods may exist that could protect against breast cancer. Myrosinase catalyzes the breakdown of a specific glucosinolate, called glucobrassicin, to indoles, including indole-3-carbinol, which has been shown to increase oxidase activity and is implicated in promoting breast cancer. According to John Potter, an epidemiologist at the University of Minnesota, a mechanism by which high intake of indoles may affect the development of hormone-related cancers involves estrogen metabolism. Animal studies indicate that indoles could cause a shift in estradiol metabolism that may protect against estrogen-related cancers, "but little research on humans in the area of glucosionolates or indoles per se and cancer has been conducted," he said.

In her human studies, Kohlmeier will test whether cabbage is working directly in the gut by binding carcinogens so that they can be excreted before being activated in the body or whether it causes an increase in excretion of carcinogens through bile.

Kohlmeier believes there are a number of under-researched, potentially chemoprotective substances in foods. If studies prove that these substances ward off cancer-promoting processes, such protective ingredients could be isolated for possible medical use.

Said Potter, "Cancer may be the result of reducing the intake of foods that are metabolically necessary--it may be a disease of maladaptation."

Organic Farming Goes Big Time

Cotton club. Organic growing methods are gaining acceptance as cotton farmers search for alternatives to chemical pesticides and defoliants.

"Going organic" is yielding unexpected success down on the farm as some brand-name corporations have decided not to use synthetic fertilizers and pesticides on much of their crop acreage. In doing so, they're challenging the idea that organic methods only work best on a small scale, and they are seeing improvements in crop quality as well as savings in pesticide-related costs per acre--without reduced yields.

California-based Gallo Vineyards is now the largest organic farm in the United States, with 6,000 of its 10,000 acres devoted to strict organic farming methods. These include mechanical cultivation to destroy weeds instead of herbicidal dustings; intercropping vineyards with nitrogen-producing peas and oats which fertilize the soil naturally; and reliance on natural predators, including spiders and ladybugs, rather than insecticides which must be applied several times a year.

In California, the leading agricultural state in the United States, where over 50% of the nation's fruits and nuts and 47% of its vegetables are produced, 50,000 acres are now certified "organic" and 20,000 more await such certification by California Certified Organic Farmers (CCOF) in Santa Cruz.

Over the last 10 years, nonchemical pest control and cultivation methods have gained wider acceptance among large and small growers nationally who must confront problems of pest resistance, a shrinking pool of federally approved pesticides, health effects of pesticide exposure among farm workers, and environmental impacts of conventional agrichemicals. "The organic area is growing," says Harold S. Ricker, staff director of the USDA's National Organic Program. "Growers are definitely serious about trying to do something about these problems."

Organic methods are also gaining respect from a number of cotton growers throughout California (and in the arid high plains of Texas), much to the surprise of skeptics who said it couldn't be done. In California, more chemicals are used on cotton than on any other crop, almost half of which are defoliants or dessicants. But some cotton growers are succeeding with organic methods such as crop rotation with legumes; reliance on beneficial insects; composting and use of cover crops as main sources of nutrients; aerial spraying of zinc to promote cotton boll maturity; and pre-harvest water cut-off to aid natural dessication.

However, the major barrier to large-scale organic cotton production in California remains a lack of effective alternatives to chemical defoliation. Conventional defoliants facilitate mechanical harvesting by eliminating leaves that may jam the picker. Defoliation also prevents chlorophyll staining from live leaves and helps reduce seed cotton moisture content, a key cause of composting during storage. Without conventional defoliants, farmers must pay for hand-labor or harvest without defoliating and risk moisture contamination.

According to Brian Baker, CCOF technical coordinator, organic cotton growers are undeterred by the obstacles. Once established, cotton can hold its own against weeds without conventional herbicides, and a program of rotation, tillage, and timely cultivation can keep hand-labor costs to a minimum. Says Baker, "To date, CCOF has certified 1500 acres with 6000 more in the pipeline and more to come." In addition, a growing market for higher-priced organically farmed cotton is helping defray the roughly 15% increase in production costs largely due to labor. Hoping to reap marketing benefits from environmental consciousness, some brand-name manufacturers are willing to pay almost twice the conventional cotton price.

Still, despite success stories, cautions have arisen against fully embracing organic farming methods. Leonard Gianessi, senior research associate at the National Center for Food and Agricultural Policy in Washington, DC, says the idea that researchers could develop a program to find effective nonchemical substitutes for all uses of chemical pesticides is not realistic. He sees increasing concern among entomologists over biological control methods, such as breeding and releasing natural predators to reduce pest populations, which may carry unrecognized risks including the possibility of insect species extinction. Gianessi also points to current uncertainties surrounding use of microbial pesticides in terms of their impact on people, animals, and the environment.

USDA's Ricker is optimistic. He says his program is focused on developing national standards for organic production, processing, and marketing. Ricker characterizes most organic growers as "serious business people who are concerned about their environment and work methods. They have demonstrated they can apply organic production techniques on a large scale and in all environments."

Ozone-Friendly Chemicals

As the federal government begins to phase out chlorofluorocarbons (CFCs) for contributing to stratospheric ozone depletion, scientists are searching for alternative chemicals that are considered "ozone friendly."

Scientists at the National Oceanic and Atmospheric Administration announced in January that extensive research on hydrofluorocarbons (HFCs) shows that they will not destroy the ozone layer as CFCs do. A. R. Ravishankra, a chemist at the NOAA laboratory, said HFCs are about 50,000 times less destructive of ozone than CFCs and remain in the atmosphere only 15 years, whereas CFCs linger for 50 years.

The NOAA studies began last March after an Oxford University scientist suggested that the fluorine in HFCs could possibly combine with carbon in the atmosphere to create a reaction that would destroy ozone. This was a "plausible speculation" that has been proven wrong.

The HFCs could possibly replace CFCs in air conditioners, refrigerators, and other mechanical cooling systems. The CFCs have also been used as industrial cleaners and as propellants in aerosol cans, though they are no longer used as propellants in the United States.

The EPA has also had success in developing substitute chemicals for CFCs. EPA scientists are looking at 11 possible candidates, and of these, two look especially promising, according to N. Dean Smith, senior project scientist in the Stratospheric Ozone Protection Branch of EPA. Both chemicals are fluorated propanes and have been undergoing testing since November by the U.S. Navy.

So far, the testing has been successful. "The research on these two is progressing at a much faster pace than we had anticipated. At this rate, they could be marketed within a couple of years," Smith said. The chemicals have already passed tests for flammability and thermaphysical properties. In tests for atmospheric lifetime, however, the results were not what the scientists had hoped for. One of the chemicals was found to have an atmospheric life of 7.8 years, which is acceptable, but the lifetime of the other chemical was determined to be 62 years, which is longer than desirable, Smith said. This figure is currently being retested. Other ongoing tests on the chemicals include those for toxicity and performance.

The urgency of the testing by the navy is due to the fact that a CFC currently used in air conditioning and cooling systems on board ships has to be phased out by the end of next year, Smith said. It appears that the two chemicals being tested by EPA have the capability of replacing CFCs in navy equipment. If either fails to be an acceptable replacement, the navy faces very inconvenient alternatives, Smith said. One would involve using another chemical such as a hydrochlorofluorocarbon, but that will also have to be phased out in time. Another choice would be to use a newly proposed substitute chemical, such as an HFC proposed by the NOAA, but the navy would have to change all of its equipment to adapt to the new chemical.

Industry is also interested in the 11 new EPA chemicals for use in chillers, heat pumps, air conditioners, supermarket food coolers, and foam blowing. Chemical companies are talking to EPA about the substitutes. If tests prove successful, chemical producers will discuss the possibility of producing large quantities of these chemicals for commercial use.

Toxic Reporting

Toxic Chemical Release
Sec. 313(d)

(1) In General.--The Administrator may by rule add or delete a chemical from the list described in subsection (c) at anytime.

(2) Additions.--A chemical may be added if the Administrator determines, in his judgment, that there is sufficient evidence to establish any one of the following:

(A) The chemical is know to cause or can reasonably be anticipated to cause significant adverse acute human health effects at concentration levels that are reasonably likely to resist beyond facility site boundaries as a result of continuous, or frequently recurrent releases.

(B) The chemical is known to cause or can reasonable be anticipated to cause in humans--

a significant adverse effect on the environment of sufficient seriousness, in the judgment of the Administrator, to warrant reporting under this section.

The EPA released a proposal January 6 that will require manufacturers to report more of the chemicals they release into the environment. EPA nearly doubled the number of chemicals on the Toxic Release Inventory list, from 320 to more than 630.

"These chemicals have been assessed for a while, for carcinogenicity, effect on the environment, and effect on human health, and it was determined that they met the criteria to be added to the list," said Gwen Brown, an EPA spokesperson.

Of the 313 new chemicals on the list, 170 are used in the production of pesticides and herbicides. The EPA plans to provide citizens with new information about their potential exposure to these chemicals.

EPA Administrator Carol Browner called the expansion of the list of chemicals "an important step forward in . . . putting people first. We believe Americans have a right to know about the toxic chemicals they are exposed to."

Manufacturing facilities have been required for the last five years to report toxic chemical emissions into the air, water, and the ground through annual TRI forms under Section 313 of the Emergency Planning and Community Right-to-Know Act. The TRI is based on acute human health effects, carcinogenicity, or other chronic hazards of the chemicals. The public can access the reports through the TRI database.

Citizens groups and environmentalists have used the reports to hold manufacturers accountable and seek emission reductions. "Citizens have used [statistics] to put a spotlight on companies and provide an incentive for them to reduce emissions," said Ed Hopkins of Public Citizen, a Washington-based advocacy group that examines the release numbers each year in an attempt to establish trends.

Among the chemicals added to the list are the widely produced compounds bromine, caprolactam, carbon monoxide, chlorinated paraffins, chlorofluorocarbons, hydrochlorofluorocarbons, man-made mineral fibers, nicotine, nitrogen dioxide, ozone, and sulfur dioxide. Several pharmaceutical ingredients that are proposed include diphenylamine, lithium carbonate, pentobarbital sodium, and tetracycline hydrochloride.

The proposed additions that are used to manufacture pesticides include benomyl, the active ingredient in DuPont's controversial fungicide Benlate. Other active ingredients of pesticides proposed for the list include alachlor, aldicarb, bromacil, diazinon, and malathion.

The proposal requires that manufacturing facilities include the additional chemicals on their 1996 TRI forms, which cover releases for 1995. After expansion of the list, EPA anticipates receiving about 26,000 more reports and hearing from 2,400 more facilities. Industry costs of reporting are projected at $155 million the first year and $85 million the second year.

EPA is also planning to require additional types of industries to report toxic emissions. "We plan later this year to announce a second phase to the list, although we are not sure of a date yet," Brown said. The second phase will include additional facilities as well as more chemicals, she said.

Currently, only manufacturers are required to submit TRI reports. The new TRI proposal will require manufacturers of pesticides to report the release of chemicals into the environment, but it will not require farmers, the major users of such chemicals, to make any reports. Environmentalists have been campaigning with EPA and Congress to hold farmers accountable for information on pesticide use because runoff from farmland is a major cause of river and lake pollution.

Climate Change Treaty

In March, the International Climate Change Treaty, which requires ratifying countries to submit detailed information on their greenhouse gas emissions and implement programs to curb such emissions, became legally binding. Under the terms of the United Nations Framework Convention on Climate Change, the treaty became binding 90 days following ratification by the 50th country, which occurred on 21 December 1993 when it was ratified by Denmark, Portugal, Spain, and the European Economic Community. The United States was one of the first countries to ratify the treaty.

Natural Carcinogens

Toxic smorgasbord? A new study will examine naturally occurring carcinogens in the diet.

Almost 14 years after the National Academy of Sciences was asked to study what chemicals should be evaluated for their potential carcinogenic risk to humans, the academy is undertaking a new study to determine which naturally occurring carcinogenic substances in food may pose similar risks.

According to Richard Griesemer of NIEHS, which is co-funding the study with EPA, questions about whether naturally occurring carcinogens are potentially as dangerous, or more dangerous, than synthetic chemicals arose in the early 1980s when the original NAS study was done and the National Toxicology Program was in its infancy. Griesemer said he believes these questions are being revisited now because "there's a relative lack of information about carcinogens that occur in nature." Griesemer said NIEHS and EPA asked NAS to do the study because "no one else has an incentive to test the things that occur naturally." The study will be conducted by the NAS's Board on Environmental Studies and Toxicology.

The study will evaluate the information currently available on naturally occurring carcinogens in the human diet and make recommendations on what chemicals should be tested. Many scientists have charged that the current scientific information available is inadequate to make regulatory decisions. Although an estimated 40% of the more than 450 chemicals that have been tested by the NTP also occur in nature, scientists testing these substances must also consider the use of the chemical, its potential for human exposure, and the degree of biological persistence in determining the type of testing that is done. Over the course of NTP testing, according to Griesemer, few substances have been nominated for testing by the Food and Drug Administration, and those that were nominated were mostly drugs.

According to David Sandler, project director for the study, the study committee is still trying to decide what categories of chemicals to include. Said Sandler, "We've been given a big charge. It is a major task to set priorities on what [the committee] wants to focus on. The issue is huge." Scientists say a wide variety of naturally occurring substances may be carcinogenic or have carcinogenic properties, including certain natural pesticides, molds, tannins, spices, fungi, and plant estrogens. Sandler said the study will probably exclude some substances that may be considered part of the diet such as water because it would be too difficult to evaluate the multitude of substances that contaminate it, and pharmaceuticals, which, although ingested, are not considered food. Some chemicals, such as teas that are used for medicinal purposes, may straddle the line.

Some scientists and EPA sources have speculated that the results of the study could spur major changes in food safety regulations. Sandler was cautious about predicting the outcome of the study. He said that the committee "wants to try to get its hands around the state of the science in hopes of giving government agencies some ideas on structuring future research." The report is expected to be released in late 1994.

Gore Urges Action

"Just do it," said Vice President Al Gore, quoting a Nike ad in his address to business leaders on the eve of Earth Day. Gore exhorted businesses to sign on to the programs in the administration's Climate Change Action Plan, what he called, "a very aggressive attempt to address the world's most important environmental threat," at a conference at George Washington University.

The conference was attended by more than 600 representatives of businesses, state and local environmental officials, community activists, congressional staff, international delegates, academics, and federal employees.

Gore quoted insurance industry reports predicting dire consequences for businesses as a result of global warming in his call for commitment by industry and others to the plan, which is based on voluntary partnerships between government and industry. Gore also called on government representatives to facilitate implementation of the programs and environmental groups to mobilize public support.

Following Vice President Gore's address, Secretary Hazel O'Leary (DOE), Administrator Carol Browner (EPA), and Deputy Secretary Richard Rominger (USDA) recognized outstanding contributions from current participants in a "Showcasing Partnerships" ceremony.

In Memoriam

Frank E. Guthrie, an award-winning entomologist and toxicologist who devoted his over 40-year career to studying the harmful effects of pesticides and other chemicals, died March 29 at the age of 71. Guthrie helped to establish the graduate program in toxicology at North Carolina State University and was responsible for obtaining about $20 million in research and training grants for the university.

Guthrie received several degrees in entomology including a BA in 1947 and an MA in 1949, both from the University of Kentucky, and a PhD in 1952 from the University of Illinois. Honors and awards received by Guthrie during his career include the 1984 Society of Toxicology Award, the 1982 Governor's Award for Science, the 1982 Outstanding Research Award of the NCSU Alumni Association, and a North Carolina Award in 1985, the highest honor bestowed by the state. Guthrie also served on the Task Force on Occupational Exposure to Pesticides for the President's Advisory Committee on the Environment.

Last Update: August 7, 1998