Craig Dees,1 Minoo Askari,2 Scott Garrett,3 Kellie Gehrs,1 Don Henley,2 C. Murray Ardies4
1Health Sciences Research Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee; 2University of Tennessee, Knoxville, Tennessee; 3Oak Ridge Institute for Science Education, Oak Ridge, Tennessee; 4Department of Biology, Northeastern Illinois University, Chicago, Illinois
Exposure to pesticides, dyes, and pollutants that mimic the growth promoting effects of estrogen may cause breast cancer. The pesticide DDT and the food colorant Red No. 3 were found to increase the growth of HTB 133 but not estrogen receptor (ER) negative human breast cells (HTB 125) or rat liver epithelial cells (RLE). Red No. 3, ß-estradiol, and DDT increase ER site-specific DNA binding to the estrogen response element in HTB 133 cells and increase cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells. Site-specific DNA binding by p53 in RLE, HTB 125, HTB 133, and MCF-7 cells was increased when they were treated with Red No. 3, which suggests that cellular DNA was damaged by this colorant. Red No. 3 increased binding of the ER from MCF-7 cells to the estrogen-responsive element. Consumption of Red No. 3, which has estrogenlike growth stimulatory properties and may be genotoxic, could be a significant risk factor in human breast carcinogenesis. -- Environ Health Perspect 105(Suppl 3):625-632 (1997)
Key words: xenoestrogen, Red No. 3, DDT, breast cancer, p53
This paper was presented in part at the Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer held 28-29 September 1995 in New Orleans, Louisiana. Manuscript received at EHP 6 June 1996; manuscript accepted 23 August 1996.
The submitted manuscript has been authored by a contractor of the U.S. Government under contract DE-AC05-96OR22464. Accordingly, the U.S. Government retains a nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for U.S. Government purposes.
Address correspondence to Dr. C. Dees, PhotoGen L.L.C., 7327 Oak Ridge Highway, Suite A, Knoxville, TN 37931. Telephone: (423) 539-9975. Fax: (423) 539-9654. E-mail:genase@aol.com
Abbreviations used: Cdk2, cyclin-dependent kinase 2; DMEM, Dulbecco's modified minimal essential medium; EMF, electromagnetic fields; ER, estrogen receptor; ERE, estrogen response element; ETOH, ethanol; FBS, fetal bovine serum; 5-FU, 5-fluorouracil; HH1, Sigma Histones Type II; NAS/NRC, National Academy of Sciences/National Research Council; PBS, phosphate-buffered saline; PMSF, phenylmethylsulfonyl fluoride; RLE, rat liver epithelial.
Last Update: April 10, 1997