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Obesity and perinatal TCDD exposure increases mammary tumors in FVB mice
Citation:
LaMerrill, M. A., L. S. BIRNBAUM, R. D. Cardiff, AND D. THREADGILL. Obesity and perinatal TCDD exposure increases mammary tumors in FVB mice. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
Because both TCDD exposure and the state of obesity interact with the estrogen pathway, we wanted to investigate how TCDD and obesity interact with mammary cancer susceptibility in a mouse model.
Description:
Risk of breast cancer has been consistently shown to correlate to total lifetime exposure to estrogens. Because both TCDD exposure and the state of obesity interact with the estrogen pathway, we wanted to investigate how TCDD and obesity interact with mammary cancer susceptibility in a mouse model. Several rat models suggest that prenatal TCDD exposure promotes chemical models of mammary cancer. Therefore, at 12.5 days post conception, we exposed nulliparous FVB females to 1 µg/kg of TCDD. To model diet-induced obesity, the litters were put on high or low fat diet at parturition. Female offspring were exposed to DMBA at post-natal days (PND) 35, 49, 53, and monitored thereafter for tumor development. Lean DMBA-treated FVB without TCDD exposure had the longest tumor latency. Obese DMBA-treated FVB had substantially more mammary tumors than lean FVB. Tumors grew faster among obese litters compared to lean. While no mammary tumors arose in lean litters perinatally exposed to TCDD and a third of unexposed obese litters had mammary tumors, every obese litter perinatally exposed to TCDD had at least one mammary tumor. Among obese mice, exposure to TCDD was associated with a doubled mammary tumors incidence. TCDD was associated with adenomyoepitheliomas, lesions that are rare in DMBA-treated mice. In summary, obesity increases the sensitivity of FVB to DMBA-induced mammary carcinogenesis. Perinatal TCDD exposure appears to further increase the sensitivity of obese FVB.