Abstract

The primary focus of our study is to investigate the biochemical and molecular defense mechanisms against carcinogens and xenobiotics in human breast cancer MCF-7 cells. The induction of neoplasm by carcinogens has been well documented in animal model, e.g. benzopyrene (BP) for liver cancer and dimethylbenzanthracene (DMBA) for mammary cancer. We chose to examine the mechanism of action of carcinogen resistance in our series of BP resistant cells. In our BP resistant cells, we found CYP1A1 activation by BP, DMBA, and TCDD was abolished. Topoisomerase II expression was enhanced with resistance. Our results suggested that the signal transduction pathway for carcinogen activation, aryl hydrocarbon receptor ( AhR) may be directly related to the carcinogen resistance. Whether AhR is also involved in BP resistant cells is under our current investigation. The detoxification mechanism in our BP resistant human breast cancer MCF-7 cells and the regulation by dietary flavonoids are other areas to be focused.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC000155-07
Application #
6160843
Study Section
Special Emphasis Panel (LNMR)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

MacDonald, Christopher J; Cheng, Robert Y S; Roberts, David D et al. (2009) Modulation of carcinogen metabolism by nitric oxide-aspirin 2 is associated with suppression of DNA damage and DNA adduct formation. J Biol Chem 284:22099-107
Ciolino, Henry P; MacDonald, Christopher J; Memon, Omar S et al. (2006) Sulindac regulates the aryl hydrocarbon receptor-mediated expression of Phase 1 metabolic enzymes in vivo and in vitro. Carcinogenesis 27:1586-92
Brantley, Eileen; Patel, Vyomesh; Stinson, Sherman F et al. (2005) The antitumor drug candidate 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole induces NF-kappaB activity in drug-sensitive MCF-7 cells. Anticancer Drugs 16:137-43
Dennis, Phillip A; Van Waes, Carter; Gutkind, J Silvio et al. (2005) The biology of tobacco and nicotine: bench to bedside. Cancer Epidemiol Biomarkers Prev 14:764-7
Loaiza-Perez, Andrea I; Kenney, Susan; Boswell, Jamie et al. (2004) Aryl hydrocarbon receptor activation of an antitumor aminoflavone: basis of selective toxicity for MCF-7 breast tumor cells. Mol Cancer Ther 3:715-25
Ciolino, Henry; MacDonald, Chistopher; Memon, Omar et al. (2003) Dehydroepiandrosterone inhibits the expression of carcinogen-activating enzymes in vivo. Int J Cancer 105:321-5