Current Highlight from September 5, 2014
Dissecting Tamoxifen Toxicity
Tamoxifen is:
- clinically invaluable to prevent recurrence of breast cancer, or occurrence of breast cancer in high risk populations
- noted to increase incidence of endometrial cancer and Non-Alcoholic Fatty Liver Disease (NAFLD) in humans
- a well-established liver carcinogen in rats, but it is not thought to be a liver carcinogen in mice
- known to cause both genetic and epigenetic changes in rats; and NAFLD changes are present
The current studies conducted at NCTR demonstrate that tumorigenic dose treatments in mice produce the same levels of genetic damage observed in rats, but epigenetic and NAFLD-associated injuries are not present; and may explain the variability of tamoxifen toxicity. These results provide additional evidence that carcinogenesis requires both genotoxic and non-genotoxic alterations and highlights the role of epigenetic alterations in carcinogenesis. (Toxicology, http://dx.doi.org/10.1016/j.tox.2014.08.004
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For additional information, please contact Igor Pogribny, Ph.D., Division of Biochemical Toxicology, FDA/NCTR.
NCTR Research Highlights Archives
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Contact FDA
870-543-7000
National Center for Toxicological Research
Food and Drug Administration
3900 NCTR Road
Jefferson, AR 72079
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