Early Life Chemical Exposures and Latent Mammary Effects in Male and Female Rats

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  • March 19, 2019
Creator
  • Filgo, Adam
    • Affiliation: School of Medicine, Curriculum in Toxicology
Abstract
  • Volatile organic compounds (VOCs) are common industrial solvents used in a number of cleaning agents and solvents. In the United States, spikes in birth defects, infant mortality, reproductive cancers and leukemia have occurred in areas with high levels of VOCs in drinking water. My thesis is focused on the effects of a VOC mixture on mammary gland development and risk for mammary tumor formation following prenatal/perinatal exposures in a 7,12-Dimethylbenz(a)anthracene (DMBA)-induced mammary tumor rat model. To gain an understanding of the animal model used in my studies, the Harlan Sprague Dawley (HSD) rat, an atlas of mammary gland development was created for both sexes, starting at embryonic day 15.5 through postnatal day (PND) 70. In addition, prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and diethylstilbestrol were used to demonstrate delayed and accelerated mammary gland growth, respectively. This atlas of mammary gland development in the HSD rat will be a key component in understanding and interpreting effects of chemicals in this rat strain. To specifically test the VOC mixture in this rat model, time-pregnant HSD rats and their offspring were given access to water containing a mixture of VOCs at concentrations 5X, 10X and 50X times those detected in contaminated drinking water at Camp Lejeune, to determine VOC body burden in both dams and pups. Mammary gland development was found to be accelerated in both sexes at the 5X and 10X concentrations. DMBA was given to VOC-exposed animals at PND 30 and tumors were recorded and collected 26 weeks after carcinogen treatment. There was a significant trend increase in adenocarcinomas arising in a fibroadenoma with VOC exposure in the females. Additionally, two malignant tumors formed in the males in the 10X exposure group and the males that died early due to tumor burden were from the 10X exposure group. These data demonstrate the ability of the VOC mixture to accelerate mammary gland development and enhanced the risk for tumor formation following carcinogen exposure. The mixture of VOCs was active at only 5-10 fold higher levels than what Marines or their mothers might have consumed, and these low level, prenatal exposure effects deserve further attention.
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  • In Copyright
Advisor
  • Travlos, Gregory
  • Weissman, Bernard
  • Troester, Melissa
  • Kaufmann, William
  • Fenton, Suzanne
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
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  • Chapel Hill, NC
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  • There are no restrictions to this item.
Date uploaded
  • June 23, 2015

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