Dietary fat and dioxin exposure increase mammary cancer incidence through Cyp1b1 and Comt expression (2008)

Undergraduates: Rachel Harper, Michele La Merrill Linda Birnbaum, Robert Cardiff

Faculty Advisor: David Threadgill
Department: Biology

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Obesity is a growing international health concern and previous research shows a consistent correlation between mammary tumor development and total lifetime exposure to estrogen. Adipocytes and TCDD alter the estrogen signaling pathway to increase mammary cancer incidence. To examine these effects we used real time PCR to analyze mRNA collected from offspring of TCDD-exposed, FVB/NJ dams. Dams were placed on high or low fat diet at birth and pups were exposed to dioxin and dietary fat through breast-feeding. The first group of female offspring were dosed with DMBA at post natal days (PND) 35, 49, and 63 to initiate tumors, and monitored for tumor development. A second cohort, treated identically, was euthanized at PND 50 and mammary gland gene expression was analyzed by real time PCR. We found that TCDD exposure and high fat diet increased mammary tumor incidence. Among mice fed a high fat diet, maternal TCDD exposure unregulated epithelial and mammary tumor Cyp1b1 mRNA and decreased Comt mRNA in mammary tissue compared to vehicle during carcinogenesis. These changes in the transcription of Cyp1b1 and Comt, likely affect estrogen metabolism. In summary, high fat diet increases the sensitivity of FVB mice to maternal TCDD exposure in DMBA induced mammary carcinogenesis. The observed increase in mammary cancer incidence may result from genotoxic estrogen-metabolite accumulation.