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Lindane and Breast Cancer

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Breast Cancer Res Treat. 2002 Mar;72(2):173-82. Related Articles, Links
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The organochlorine pesticide residues and antioxidant enzyme activities in human breast tumors: is there any association?

Iscan M, Coban T, Cok I, Bulbul D, Eke BC, Burgaz S.

Department of Toxicology, Faculty of Pharmacy, Ankara University, Turkey.

The levels of some organochlorine pesticides (OCP)s (hexachlorobenzene, HCB, alpha-hexachlorocyclohexane, alpha-HCH, beta-HCH, gamma-HCH, heptachlorepoxide, HE, bis (4-chlorophenyl)-1,1-dichloroethene, p.p'DDE, bis (4-chlorophenyl)-1,1,1-trichloroethane, p.p' DDT and total DDT (E-DDT) and antioxidant enzyme activities namely Cu, Zn superoxide dismutase (SOD), catalase (CAT), selenium-dependent glutathione peroxidase (Se-GSH-Px), total glutathione peroxidase (T-GSH-Px), selenium independent glutathione peroxidase (GSH-Px II), glutathione reductase (GRd), level of reduced glutathione (GSH) and lipid peroxidation (LP), glutathione S-transferase (GST) activity toward several substrates including 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EAA), 1,2-epoxy-3-(p-nitrophenoxy)-propane (ENPP) were measured in tumor and surrounding tumor free tissues of 24 female breast cancer patients and was evaluated whether there exist any association between the levels of OCPs and antioxidants. The mean levels of GSH, alpha-BHC, gamma-BHC and HE, and activities of SOD, Se-GSH-Px, T-GSH-Px, GSH-Px II,GRd, GST CDNB, and GST DCNB were significantly higher in tumors than in controls. In tumors, significant correlations were noted between: SOD and y-BHC; Se-GSH-Px and gamma-BHC; T-GSH-Px and gamma-BHC; GSH-Px II and alpha-BHC, gamma-BHC; GSH and alpha-BHC, gamma-BHC, HE; GRd and alpha-BHC; CDNB GST and alpha-BHC, gamma-BHC. These results show that free-radical mediated oxidative stress is, at least partly, associated with some of these OCP residues in human breast tumors.

PMID: 12038708 [PubMed - indexed for MEDLINE]


Lindane and breast cancer - Why take risks?

Between 1984 and 1994, seven international studies compared levels of organochlorines and other persistent chemicals in women with and without breast cancer. Four of the studies found higher levels in women with breast cancer, one did not and two were inconclusive. This prompted the idea first put forward by Devra Lee Davis and H. Leon Bradlow, two senior researchers at New York's Strang-Cornell Cancer Research Laboratory, that lindane is implicated in the growing incidence of breast cancer. Their theory is based on the concept that the OC pesticides and some other persistent chemicals such as polychlorinated biphenyls (PCBs) are capable of mimicking estrogen and thus of seriously disrupting the body's natural hormonal actions. The effects of these 'estrogenic' chemicals have also been associated with lower sperm counts in men and a range of reproductive abnormalities in wild fish and mammals.

Every year in Britain about 30,000 women and a few hundred men find a breast lump which proves to be malignant. Breast cancer is the most common type of cancer in women in the UK, England and Wales have the highest death rates from breast cancer anywhere in the world. While the disease clearly predates the introduction of organochlorine chemicals, rates have more than doubled this century and continue to rise between one and two percent each year.

A clear relationship between estrogen and breast cancer has been established in many studies6, thus giving rise to a theoretical mechanism by which estrogenic properties of lindane could increase breast cancer risk. Breast cancer, like other malignancies, occurs when a cell replicates abnormally and multiplies rapidly. It seems that estrogens from outside the body can combine with its natural estrogens to change the rate of multiplication of cells.

The World Health Organization has acknowledged that ninety percent of the lindane in our bodies comes from diet and it is known to accumulate in body fat where it increases with time.8 Even the fetus is exposed to lindane through intake of the chemical by its mother and it has been detected in virtually all breast milk. The extent to which we, at the top of the food chain, may be affected by bio-accumulation of organochlorines from relatively tiny amounts in primary foods can be seen from a simple food chain analogy of water, plankton and fish. Levels in plankton can be thirty times higher than those in the water, while in the fish feeding on the plankton they can be over thirty thousand times higher.9

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Xenoestrogens and Breast Cancer:
Nowhere to Run

By Luita D. Spangler

In 1990, Elihu Richter and Jerry Westin, two environmental specialists from Hebrew University's Hadassah School of Medicine, discovered a surprising glitch in otherwise universally depressing breast cancer statistics. They found that in the decade between 1976 and 1986, Israel was unique among 28 counties surveyed in that it actually registered a significant drop in breast cancer mortality. This was in spite of increasing risk factors in the Israeli population, such as per capita fat intake and increasing patterns of delayed pregnancy, and previous Israeli breast cancer rates that paralleled the international epidemic. As Westin noted, "All and all, we expected a rise in breast cancer mortality of approximately 20% overall, and what we found was that there was an 8% drop, and in the youngest age group, the drop was 34%, as opposed to an expected 20% rise. So if we put those two together, we are talking about a difference of about 50%, which is enormous."

Westin and Richter eventually connected this drop in breast cancer mortality to a 1978 Israeli ban on the use of three organochlorine pesticides (a ban, by the way, that was opposed by the Israeli cancer establishment). Prior to 1978, alpha-benzene hexachloride (BHC), gamma benzene hexachloride (lindane) and DDT were used heavily in Israeli cowsheds. As a result, the three pesticides heavily contaminated milk and milk products, at rates between 100 and 1,000 times greater than in the U.S., national public outcry resulted in legislation prohibiting these three pesticides.

Critics quickly challenged this suggested connection between breast cancer mortality and pesticide exposure, claiming that since most environmentally-induced cancers take at least twenty years to develop, the drop in mortality happened too quickly to associate with the prohibition of the three pesticides. In reply, Westin and Richter explained that organochlorine pesticides are "complete" carcinogens, which both initiate and promote tumor growth, and whose presence (or absence) can change cancer statistics quite rapidly.

Actually, animal experiments conducted back in the 1960's proved that organochlorine pesticides caused breast cancer in rats.

Pesticides and breast cancer

In Lincolnshire the breast cancer rate is 40% higher than the rest of Britain. It is being blamed on the widespread use of the pesticide lindane, mainly used on sugar beet crops. It is a known carcinogen and is completely banned in several countries. In Britain it is approved for use on fruit and vegetables, cereals, beans, sugar beet and oilseed rape. It is also used on trees, grass, in grain stores and insect repellents.
In the past, residues of lindane have been found both in cow's milk and human breast milk.
(Health Guardian 1.9.95 p. 3)
Edited from Environment & Health News Vol. 1. Issue 3. p.2

Organochlorines and Breast Cancer


The relationship between organochlorine compounds and breast cancer is a controversial issue. We found original articles, reviews and opinion papers on this topic, including a summary of information presented at the "Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer" held September 1995 in New Orleans (published in Environmental Health Perspective 105, Supplement 3, April 1997). We selected those papers that included comprehensive summaries of the evidence gathered so far, as well as some documents written by experts in this field. Obviously the evidence published so far is not conclusive. The two reviews by the Swedish group are probably the most comprehensive and updated. We found the most recent and relevant manuscript from authors that are well-recognized in this field including D. Davis, M. Wolff and S. Safe. We did not find regional or Canadian original studies on this issue, but rather a review by Houghton and Ritter from Guelph. Finally, the Cape Cod experience seems to be an interesting model for an ecologic approach to study breast cancer clusters. We will continue updating our list of selected articles as these issues unravel with new reports.

Risk Assessment of Breast Cancer in Women Due to Exposure to Organochlorines


Although the claim made by Krieger et al (1994) that exposure to organochlorines are not a risk factor for developing breast cancer could not be verified using risk analysis techniques, various trends among selected co-factors were consistent overall with previous studies. The body of research regarding exposure to DDT is beginning to suggest that there is a notable trend positively linking it to breast cancer incidence; a finding that runs contrary to the Krieger conclusion. In vitro studies have explored mechanisms that would allow DDT to promote the generation of new cells resulting in cancerous tumors.  The link between PCB exposure and breast cancer is more complex. Future research needs to be focused on specific groups of PCB congeners whose behavior may be cancer promoting, protective, or neutral with respect to cancer. If studies, such as the Krieger study, only analyze for total PCBs then it is very probable that mixtures of all three types of PCBs are present and may cancel each other out. Because organochlorines are so persistent and pervasive in the environment, there is the potential for a large public health risk. The results of more PCB congener-specific studies are eagerly anticipated.

Organic Pollutants

by Gina M. Soloman, MD, MPH


Hoyer AP et al. Organochlorine exposure and risk of breast cancer. Lancet 1998; 352:1816-1820

In 1976, researchers obtained blood serum samples from 7712 women who participated in the Copenhagen City Heart Study. Over the intervening two decades, 240 women in the study who had serum samples later developed breast cancer. The stored serum of these cases and of 477 controls was analyzed for organochlorine pesticides with suspected estrogenic properties (lindane, chlordane, DDT, DDE, Beta-hexachlorocyclohexane, and dieldrin), and for PCBs. All women had measurable concentrations of DDT metabolites in their serum, 90% had detectable PCBs and Beta-HCH, and 78% had detectable dieldrin residues, even though all of these chemicals had been banned for decades in Denmark. The risk of breast cancer was more than twice as high in women with the highest serum concentrations of dieldrin compared with those with the lowest concentrations. A statistically significant dose-response relationship was found between dieldrin and breast cancer. Furthermore, the cancers in the women with higher dieldrin levels were more aggressive. Some association was also seen between Beta-HCH and breast cancer risk, but no association was found between PCBs, DDT metabolites, or any of the other pesticides and breast cancer.



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