The link between the insecticide heptachlor epoxide, estradiol, and breast cancer.

Given the suspected effects of estrogens on breast cancer, xenoestrogenic insecticides may be a risk factor. Studies of the weak xenoestrogen, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), have failed to demonstrate a causal relationship, though another estrogenic organochlorine insecticide, dieldrin, belonging to the cyclodiene family, has recently been linked to breast cancer. Other cyclodienes such as heptachlor epoxide (HE) and oxychlordane (OC) present in breast tissue have not been evaluated as rigorously, presumably due to their lower concentration and lower recovery using solvent extraction procedures. We used sparging extraction coupled with gas chromatography to determine the levels of HE, OC, and DDE in adipose tissue within breast biopsies in a series of 34 women evaluated for breast abnormality. Of the three insecticides tested, only HE (p=0.007) was positively associated with prevalence of breast cancer in the biopsies. In rapid, non-genomic studies using isolated human leukocytes, flow cytometric methods were used to measure HE-induced oxidants and DNA damage. These studies indicated that HE, at concentrations similar to those in breast biopsies, induced an inverted-U increase in intracellular oxidants and DNA strand breaks [both blocked by specific nitric oxide- (NO-) synthesis blockade withL: -NMMA] in human polymorphonuclear leukocytes (PMNs). HE-treated PMNs also induced damage to surrounding lymphocytes in mixed-leukocyte incubations (also inhibited by NO blockade). The HE-induced changes in NO were inhibited by 17beta-estradiol-(17beta-E2) receptor antagonists and were mimicked by similar concentrations of 17beta-E2. The addition of tumor necrosis factor-alpha (TNF-alpha) increased intracellular oxidants and DNA damage and shifted the responses to lower HE concentrations. This study, along with others, suggests that HE-induced NO production may contribute to initiation, promotion, and progression of cancer.

Evaluation of human exposure to the heptachlor epoxide contamination of milk in Hawaii.

The commercial milk supply on Oahu was contaminated by heptachlor epoxide for as long as 15 months during 1981-82 at levels possibly as high as 1.2 ug/g, fat basis. Following the contamination, several investigators attempted to evaluate potential adverse health outcomes, especially among infants and young children. However, results of the initial investigations are inconclusive due to lack of reliable measures of heptachlor exposure, use of non-random sampling techniques, and lack of definitive health outcomes attributable to heptachlor epoxide. The design of a current study to assess the body concentrations of heptachlor epoxide and related pesticides in Hawaii is presented. The study is designed (1) to relate these concentrations to prior exposure via the milk contamination, and (2) to assess the reliability of breast milk and serum pesticide concentrations as objective biological markers of body burden. No attempt is made to relate these data to health outcomes; instead, the findings may provide the foundation for future health studies or surveillance of environmental exposure to pesticides in Hawaii.