Ah Receptor Activation Delays Development of Chemical-Induced Mammary Tumors
Beth A. Vorderstrasse, Ph.D.
Washington State University
NIEHS Grant R21ES014422
In a somewhat surprising finding, NIEHS-supported investigators report that exposure to tetrachlorodibenzo-p-dioxin (TCDD) prior to exposure to the known mammary tumor promoter dimethylbenz[a]anthracdene (DMBA), delays the development of breast cancer in mice and produces a lower overall incidence of breast tumors. The researchers conclude that the effect is caused by activation of the Ah receptor by TCDD.
The Ah receptor has been studied extensively because of its role in the toxic effects of dioxin-like compounds. However, recently there have been numerous reports that the receptor is involved in normal development, carcinogenesis, and cell cycle regulation.
Previous work has suggested that exposure to TCDD during pregnancy causes impaired mammary gland growth and development. Normal pregnancy-induced mammary differentiation has been shown to be protective against breast cancer. The investigators' initial hypothesis was that TCDD exposure would make the mice more susceptible to DMBA-induced tumor development.
In both pregnant and non-pregnant mice, TCDD treatment prior to exposure to DMBA caused a four-week delay in tumor formation and a lower tumor incidence through-out the six month study. No markers for tumor initiation differed between TCCD-treated and control mice. These findings suggest that Ah receptor activation causes the delay in tumor formation and could provide an opportunity for possible therapeutic interventions.
Citation: Wang T, Gavin HM, Arlt VM, Lawrence BP, Fenton SE, Medina D, Vorderstrasse BA.Aryl hydrocarbon receptor activation during pregnancy, and in adult nulliparous mice, delays the subsequent development of DMBA-induced mammary tumors. Int J Cancer. 2011 Apr 1;128(7):1509-23.
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