Guest guest Posted August 14, 2005 Report Share Posted August 14, 2005 Xenoestrogens and Women's Health Aug 13, 2005 18:44 PDT ===================================================================== by Sandra Steinbraber and Kathryn Patton Manufactured from cholesterol by a woman's ovaries each month, the hormone called estrogen circulates in he blood, passes easily in and out of all organs and tissues and is eventually metabolised by enzymes in the liver Certain tissues in a woman's body, however, contain rceptors that " latch " onto " estrogen molecules " as they float through her body. During the few hours when estrogen molecules are bound to the receptors, the cells of these " target tissues " are stimulated to " proliferate " . The cells of the vagina, the uterus and the breast all contain large numbers of estrogen receptors. In the " presence " of estrogen, they grow. A few years ago, cell biologist Dr. Ana Soto was working out the biochemical details of estrogenm sensitivity -- and its relationship to breast cancer when something puzzling happened in her Tufts University laboratory. Tissues growing in plastic dishes containing no estrogens started proliferating. " This indicated that some type of contamination had occurred, " Soto remembered. " We made an accidental discovery. " Soto traced the contamination to the " plastic " tubes-- she was using to store blood serum. Working with her colleague Carlos Sonnenschein, Soto purified the contaminant-- and identified it as " nonylphenol " , a chemical added during the " manufacture " of plastic to prevent it from cracking. They discovered molecules of nonylphenol were being shed from the tubes into the serum. Soto and Sonnenschein went on to prove that nonylphenol is " estrogenic " - that is, --it " mimics " the " effect " of estrogen when added to tissues containing " estrogen receptors " . In a series of experiments published in 1991, Soto demonstrated that human breast tissue proliferates in the presence of nonylphenol, possibly placing it on the path to " tumour formation " . Soto and Sonnenschein's research is now focused on quantifying the " estrigenicity " of nonylphenol and other substances. These chemicals are being termed xenoestrogens: " substances foreign to the human body that, directly or indirectly, *act* like estrogens " . Xenoestrogens are a hot area of research right now among biochemists,epidemiologists, cancer researchers and endocrinologists. Because of their ability to interfere with the " normal process " of " hormonal regulation " in women's bodies, xenoestrogens are being implicated in many " reproductive disorders " , ranging from infertility and endometriosis to breast and ovarian cancer. And, as increasing numbers of chemicals are demonstrated to " function " as xenoestrogens, scientists are beginning to learn just how amazingly " estrogenic " the " industrialised world " is. Nonylphenol,for example, is not only found in plastic but is also an " additive " in detergents and pesticides. According toSoto, over 450 million pounds of nonylphenols are produced each year. Nonylphenol is also an ingredient in spermicides. The banned pesticide DDT is a xenoestrogen. So is the unbanned pesticide endosulphan. So is atrazine, the most commonly used weed killer in US cornfields. So is DES, the druggiven to millions of women from 1948 to 1972 to prevent miscarriages (which it didn't). And so are dozens of different combustion products emitted from coal-burning power plants and " automobile exhaust " pipes. To understand the impact of xenoestrogens on women's health - we have discovered through our investigation - one has to become a bit of an endocrinologist, chemist, and historian. Like all steroid hormones (primarily " reproductive related " hormones), estrogen has a " backbone " made up of 17 carbon atoms arranged as three hexagons interlocked with a pentagon. Estrogen can exist in one of several modified forms, and each form has its own chemical name. The most " potent " form produced by the ovaries is called " estradiol " . Blood levels of estradiol rise steadily during the first half of a woman's menstrual cycle. All cells of the body are " permeable " to estradiol. However, most estradiol is carried in the blood on special " sex-hormone binding " proteins. These carrier proteins " regulate " and slow down the entry of estradiol molecules into surrounding tissues. This feature turns out to be important because many xenoestrogens are not carried on these molecules and can therefore enter cells " more quickly " and at low concentration. When estradiol enters the cell of a target tissue such as the breast or the lining of the uterus and is bound by an estrogen receptor, the story becomes more mysterious. Just 10 years ago, scientists learned that these " receptors " are themselves attached to the coiling strands of DNA where our genes lie like beads on a string. When attached to estradiol, the receptor triggers a change in " gene expression " . Depending on the type of tissue, some genes may be turned on; different proteins may be manufactured; the rate of cell division may accelerate. The exact mechanisms ofaction is still an ongoing subject of research. What is known for sure is that at some point, the receptor is " processed " and the estrogen molecule released. Meanwhile, in the liver, estradiol molecules carried in by the bloodstream are broken down. There are two different chemical routes that estradiol molecules can take here. The first one alters carbonatom number 2 and converts estradiol into a compound called 2-hydroxyestrone. The second pathway alters carbon atom number 16, producing a metabolite called 16-beta-estriol. The proportion of 2 to 16 turns out to be critical. The 16-metabolite is still estrogenic: it can " recirculate " through a woman's body and " bind " to estrogen receptors just like its parent, estradiol. Moreover, it is capable of " directly damaging " the DNA strand. In contrast, the 2-metabolite is minimally estrogenic and is non-toxic to DNA. Clearly, a low 16 to 2 ratio is desirable. Some xenoestrogens act to skew this balance away from 2 and towards the 16 pathway, as we shall see. Now enter xenoestrogens. And to explain their entry, we need a bit of chemical history During World War II, legions of organic chemists were put to work by their governments to solve wartime problems. The pesticide DDT, for example, was perfected and developed as a means to control body lice and, therefore, typhus. Herbicides 2,4-D and2,4,5-F were developed as chemical defoliants for fighting jungle warfare. These new chemicals were synthetic, meaning they are " derived " from petroleum and " manufactured " in a laboratory. Whole new classes of chemicals not found in nature were thus created. Organochlorines, of which DDT and PCB's are two, are made by attaching chlorine atoms to carbon chains, for example. While chlorine and carbon are common elements of the natural world, they are almost never found bonded together. At the end of the war, the US government helped the petrochemical industry to find private markets for their products. DDT was used for mosquito and agricultural pest control. Chemical defoliants were used in national forests to control shrubs. Lawn, garden and household insecticides were developed. Detergents replaced soaps. Plastics replaced celluloid. --- And 50 Years Later</STRONG Because they derive from oil, most of these synthetic products are, like steroid hormones, " fat-soluble " . This means that, rather than leaving the body (as they would if they were water-soluble), these synthetic products " accumulate " in areas of the body where fat content is high - for example, breasts. Moreover, any of them, like " steroid hormones " , consist of interlocking hexagonal rings of carbon atoms. Given that these new chemicals shared these properties with steroid hormones, one might reasonably wonder why their potential to " wreak havoc " with our reproductive systems was not considered sooner. There are doubtless many reasons. Sexism would be one starting point. The prevailing ideology of the Cold War would be another. Rachel Carson was one of the first scientists to raise questions about DDT. Her 1962 book, Silent Spring, was accused by industry chemists of threatening the Free World's food supply. But yet another answer resides in the nature of estrogenicity itself: it is a far sneakier concept than even many scientists concerned with the issue had imagined. First, the estrogen receptor is turning out to be far less specific than anyone imagined. Carbon compounds quite different-looking from estradiol are able to " attach " to it. Soto points out that scientists cannot " predict " whether a chemical can attach to estrogen receptors purely from the shape of the molecule. Estrogen receptors are like locks that " accept " many different keys. DDT for example, has only two hexagonal rings and yet is able to bind directly to the receptor. Second, xenoestrogens have many modes of operation. Not all of them latch on to estrogen receptors. Some simply stimulate the " manufacture " of more estrogen receptor molecules. More receptors mean an amplified response to the estradiol naturally floating through a woman's body, which may place her at a higher risk for breast cancer. Still other xenoestrogens act in the liver to accelerate the metabolism of estradiol toward the 16-metabolite and away from the 2 pathway. More 16-beta-estriol means more " bio-available " estrogen and more damage to DNA. The weed killer atrazine seems to have this effect. The first clue that estrogens might play a role in breast cancer came in 1896 when a British surgeon reported that removal of the ovaries sometimes caused breast tumours to shrink. Since then, many different studies indicate that a woman's risk of breast cancer is related to her lifetime exposure to estrogen. Early first menstruation, late menopause, and late or no childbirth are all considered risk factors. However,these factors explain only a portion of the increasing rates of breast cancer, which in North America has nearly tripled since 1950. The first well-documented study that established a preliminary link between pesticide exposure and breast cancer came only recently. InApril 1993, 31 years after the publication of Carson's Silent Spring, biochemist Dr. Mary Wolff at Mount Sinai School of Medicine in New York reported that women diagnosed with breast cancer had significantly higher concentrations of DDT in their blood than women without breast cancer. At the same time, other researchers began reporting their results on how DDT and estrogen affect the growth of breast cells in laboratory cultures. Dr. Leon Bradlow at Cornell University reported at a breast cancer conference in October 1995 that pesticide residues induce " anchorage independence " in breast tumour cultures. This means that tumour cells can continue dividing even when detached from other cells, a feature that allows breast cancer to spread in the body. Wolff and Bradlow are currently collaborating on a project that investigates exactly how xenoestrogens like DDT place breast tissue on the pathway to tumour formation. Soto is presently working on developing an assay that would allow a woman's total body burden on xenoestrogens to be measured. This may provide the most comprehensive indicator to date of the relationship between environmental estrogens and breast cancer. Recent studies also link xenoestrogens to ovarian cancer. Because the raw material for estrogen production is cholesterol, the ovary, like the breast, is a repository of fat-soluble contaminants. Dioxin, for example, has been found in the fluid surrounding human eggs extracted for test-tube fertilisation. Studies done in 1989 showed that estrogen " increases " the " rate of growth " of " ovarian tumour cells " by 50% compared to those not treated with estrogen. In the same year, Italian researchers studying the health and habits of women farmers in northern Italy discovered that women farmers exposed to triazine herbicides, such as atrazine, had a three- to- four-times higher risk for ovarian cancer. Both these lines of research suggests that triazine herbicides may be acting as xenoestrogens in the ovaries, a hypothesis that has been supported by more recent research. However, many of the existing reports suffer from small sample sizes, difficulty determining actual exposures, and lack of control groups. Further research on the precise actions of herbicides in the ovaries is also needed.In the meantime, what should the fate of triazine herbicides by? Germany banned the agricultural use of atrazine in 1991. In the Midwestern United States, atrazine continues to run off farm fields and into ground and surface water. Much of what is known about xenoestrogens' impact on fertility and reproduction comes from animal studies. Wildlife biologist Dr. Theo. Colburn had conducted long-term and intensive studies of animals living in the Great lakes Basin. This are is highly contaminated with organochlorines from chemical industries and pulp and paper mills, which use great amounts of chlorine bleach. He research documents that many animal species living near water - eagles, mink, fish and various shore birds - are unable to reproduce successfully due to high body burdens of various xenoestrogens.Colburn is currently at work on elucidating what she calls " the human/wildlife connection " . She is particularly interested in considering a possible link between estrogenic pollutants and falling sperm counts in men. She also suspects xenoestrogens could be contributing to the 400% increase in ectopic (outside the uterus) pregnancies between 1970 and 1987 - A separate line of research is focused on xenoestrogens and endometriosis. This disease causes pieces of the uterine lining to attach and grow outside the uterus, causing pain and often infertility. Exposure to PCB's has been shown to cause endometriosis in female monkeys. In November 1995, researchers reported that monkeys exposed to dioxin also develop significantly higher levels of endometriosis. Dioxin is a contaminant in many pesticides and is also formed during many industrial processes that use chlorine. Strangely enough, unlike other xenoestrogens, dioxin seems to counteract rather than magnify the effects of estradiol. Some researchers believe that dioxin may " blockade " the estrogen receptors, preventing estrogen molecules from attaching. The US Environmental Protection Agency is planning further research on the possible link between dioxin and endometriosis in women. The flurry of research interest now surrounding xenoestrogens did not just develop on its own. Indeed, most scientific investigations do not just happen. Which questions are deemed important, which projects receive funding, which studies are followed up - these are all political issues. In the case of xenoestrogens, many environmental and women's health activists have been at work behind the scenes - and sometimes in the streets - to insist that particular questions be asked and answered. For example, the Endometriosis Association, a women's advocacy group, sponsored the study on dioxin mentioned above. In October 1995, Long Island activists convened their own scientific conference on breast cancer and the environment. In the same month, the American Public Health Association called for the elimination of chlorine in manufacturing, citing its' role in the creation of xenoestrogens and the threat to women's health. There are other signs of change. Breast cancer activists in San Francisco succeeded in adding a panel on breast cancer and the environment to the program at the annual meeting of the American Association for the Advancement of Science in February 1994. Green peace and the Women's Environment and Development Organisation (WEDO) headed by Bella Abzug, recently met with women's health activist in Austin, Texas, to launch a joint initiative called " Women, Cancer and the Environment " . Ana Soto's accidental discovery and her subsequent research shed light on possible environmental intervention to prevent breast cancer. Soto said she hoped that her work will help develop a more ecological view of human health, understanding that pollutants in water, soil, air - and even plastic tubes - eventually find their way into our bodies. " Molecular biology is not enough. We can't understand the additive effects of xenoestrogens by only looking at genes... Banned pesticides are still found in the fish that we eat. " Sandra Steingrabe is a visiting scholar at North-eastern University with a PhD in biology. She is the author of " Post Diagnosis " , a book of poetry on women's cancers, and is currently writing a book on cancer and the environment to be published by Addison Wesley in 1996. Kathryn Patton has participated in cancer research projects at the University of Washington Medical Centre and is considering a career in oncology. Reprinted from Sojourner: The Women's Forum. Subscription is $21 per year for 12 issues. 42 Seaverns Avenue, Boston, Massachusetts USA 02130. --- Post subject: What is the Connection between Chemicals & Breast Cancer -- State of the Evidence: What is the Connection between Chemicals & Breast Cancer? edited by Nancy Evans © 2003 by The Breast Cancer Fund and Breast Cancer Action EXECUTIVE SUMMARY B reast cancer rates have been climbing steadily in the United States and other industrialized countries since the 1940's. Billions of dollars have been spent in an effort to stem this unrelenting tide, yet more than 50 percent of breast cancer cases remain unexplained by the characteristics and risk factors associated with the disease. Ionizing radiation is the only proven environmental cause of human breast cancer. But powerful circumstantial evidence indicates that some of the 85,000 synthetic chemicals in use today are responsible for many of the unexplained cases of the disease. While scientists have not yet developed an ideal method for linking chemical exposures to breast cancer, several types of research - experimental, body burden and ecological studies - provide " strong evidence " of the " connection " between chemicals and breast cancer. Because the types of evidence vary, the strength of the evidence linking chemicals and breast cancer also varies. The strongest evidence linking chemicals to breast cancer -- based on the fact that lifetime exposure to natural estrogens increases the risk of breast cancer -- concerns natural and synthetic estrogens, including drugs like diethylstilbestrol (DES), plastic additives like bisphenol-A (BPA), polyvinyl chloride (PVC) (found in many consumer products), dieldrin and some pesticides. Other synthetic substances strongly linked to breast cancer through experimental evidence are: organic solvents (used in many manufacturing processes, including the manufacture of computer components), polycyclic aromatic hydrocarbons (PAHs) (created in soot and fumes from burning diesel, fuels or cigarettes) and 1,3 butadiene (a by-product of internal combustion engines). There are also chemicals for which the evidence indicates a probable but less certain link to breast cancer. These chemicals include dioxin (created when plastics or other materials containing chlorine are burned), the pesticide DDT (dichloro-diphenyl-trichloroethane) and its metabolite, DDE and PCBs (polychlorinated biphenyls), previously used in the manufacture of electrical equipment and other industrial and consumer products. Finally, there is evidence of chemicals that affect how the body functions in ways that suggest a possible " link " between these substances and breast cancer. These chemicals include the insecticide heptachlor and phthalates, used to make plastic soft and flexible. We clearly have major gaps in our current knowledge about the links between breast cancer and the environment. Therefore, we need to focus our research efforts in areas that are most likely to provide useful information for framing public policies related to chemical exposures and our health. The types of research most likely to produce useful evidence will be those examining: (1) workplace exposures, (2) household exposures and (3) breast milk as a marker for human contamination. While we pursue the research that will lead to more definitive answers, the existing evidence linking chemicals to breast cancer demands that we act now as a society to begin removing many of these substances from our environment. Considerable resources are spent encouraging women to make changes in their personal lives in an effort to reduce their risk of breast cancer. But breast cancer is not just a personal tragedy; it is a public health crisis that demands action by society as a whole. This crisis must be addressed by beginning now to implement the precautionary principle. Under this principle, evidence of harm, rather than definitive proof of harm, is the trigger for policy action. In addition, the precautionary principle mandates that the burden of proof with regard to chemicals rests with the manufacturers to demonstrate that the substances are safe, rather than with the public to show that they are harmful. Finally, the precautionary principle rests on the democratic principle that government officials are obligated to serve the public's interest in human health and environmental protection. The following 5-point plan will help us reduce the risk of breast cancer and ultimately end the epidemic: PHASE OUT TOXIC CHEMICALS that are omnipresent in the lives of so many people. ENACT " SUNSHINE " LAWS AND ENFORCE EXISTING ENVIRONMENTAL PROTECTION LAWS to reduce the use of toxics by requiring companies to report how many tons of chemicals they use. PRACTICE HEALTHY PURCHASING, with local, state and federal governments leading the way in purchasing environmentally preferable products, thereby creating an example for individuals to follow. OFFER CORPORATE INCENTIVES that encourage businesses to eliminate the use of harmful chemicals in their products and processes. MONITOR BREAST MILK, through a comprehensive community program that identifies the chemicals present in breast milk, establishes links to geographic areas and initiates a plan to eliminate these contaminants. We ignore at our peril the increasing evidence that chemicals are contributing to the rising tide of breast cancer. The obligation to understand this evidence, and begin to address it through the implementation of public policies that put health first, rests with all of us. It is in our power to change the course we are on. Now is the time. TABLE OF CONTENTS Evidence that Chemicals Cause Breast Cancer Evidence Indicating a Probable Link Between Chemicals and Breast Cancer http://www.breastcancerfund.org/environment_evidence_main.htm _________________ JoAnn Guest mrsjo- www.geocities.com/mrsjoguest/Genes AIM Barleygreen " Wisdom of the Past, Food of the Future " http://www.geocities.com/mrsjoguest/Diets.html Quote Link to comment Share on other sites More sharing options...
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