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Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offspring. Sexually mature FVB-MMTV/neu female mice were treated with vehicle (corn oil), or dieldrin (0.45, 2.25, and 4.5 microg/g body weight) daily by gavage for 5 days prior to mating and then once weekly throughout gestation and lactation until weaning. Dieldrin concentrations were selected to produce serum levels representative of human background body burdens, occupational exposure, and overt toxicity. Treatment had no effect on litter size, birth weight or the number of pups surviving to weaning. The highest dose of dieldrin significantly increased the total tumor burden and the volume and number of tumors found in the thoracic mammary glands. Increased mRNA and protein expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors from the offspring of dieldrin treated dams. This study indicates that developmental exposure to the environmental contaminant dieldrin causes increased tumor burden in genetically predisposed mice. Dieldrin exposure also altered the expression of BNDF and TrkB, novel modulators of cancer pathogenesis.

Epidemiological evidence suggests that exposure to the pesticide dieldrin, is associated with increased risk of breast cancer and mortality. We hypothesize that dieldrin promotes breast cancer by increasing survival of breast cancer cells. The aims of this study were to measure the effect of dieldrin on survival of breast cancer cells and the expression of tyrosine kinase B (TrkB), a suppressor of anoikis (apoptosis triggered by inappropriate anchorage). The human breast cancer cell line MDA-MB-231 was treated with dieldrin and proliferation, viability and resistance to anoikis were measured. TrkB expression was measured by Western blot in lysates and by immunohistochemistry in human tissue specimens. Dieldrin increased resistance to anoikis and TrkB expression. TrkB was expressed in a subset of high-grade breast carcinoma specimens. Our results demonstrate that dieldrin increases resistance to anoikis and expression of TrkB and show for the first time TrkB protein expression in human breast cancer.