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Environ Health Perspect. 1997 April; 105(Suppl 3): 625–632.
PMCID: PMC1469907
Research Article

Estrogenic and DNA-damaging activity of Red No. 3 in human breast cancer cells.


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, beta-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.

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Selected References

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  • Marshall E. Epidemiology. Search for a killer: focus shifts from fat to hormones. Science. 1993 Jan 29;259(5095):618–621. [PubMed]
  • Elixhauser A. Costs of breast cancer and the cost-effectiveness of breast cancer screening. Int J Technol Assess Health Care. 1991;7(4):604–615. [PubMed]
  • Harris JR, Lippman ME, Veronesi U, Willett W. Breast cancer (1) N Engl J Med. 1992 Jul 30;327(5):319–328. [PubMed]
  • Willett WC. Diet and health: what should we eat? Science. 1994 Apr 22;264(5158):532–537. [PubMed]
  • Stone R. Environmental estrogens stir debate. Science. 1994 Jul 15;265(5170):308–310. [PubMed]
  • Davis DL, Bradlow HL, Wolff M, Woodruff T, Hoel DG, Anton-Culver H. Medical hypothesis: xenoestrogens as preventable causes of breast cancer. Environ Health Perspect. 1993 Oct;101(5):372–377. [PMC free article] [PubMed]
  • Berthois Y, Katzenellenbogen JA, Katzenellenbogen BS. Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2496–2500. [PubMed]
  • Krieger N, Wolff MS, Hiatt RA, Rivera M, Vogelman J, Orentreich N. Breast cancer and serum organochlorines: a prospective study among white, black, and Asian women. J Natl Cancer Inst. 1994 Apr 20;86(8):589–599. [PubMed]
  • Dewailly E, Dodin S, Verreault R, Ayotte P, Sauvé L, Morin J, Brisson J. High organochlorine body burden in women with estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1994 Feb 2;86(3):232–234. [PubMed]
  • Jobling S, Reynolds T, White R, Parker MG, Sumpter JP. A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ Health Perspect. 1995 Jun;103(6):582–587. [PMC free article] [PubMed]
  • Dees C, Travis CC. Increased p53 site-specific DNA binding in cells producing mutant p53. Cancer Lett. 1995 Sep 25;96(2):225–231. [PubMed]
  • Kumar V, Chambon P. The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer. Cell. 1988 Oct 7;55(1):145–156. [PubMed]
  • Tishler RB, Calderwood SK, Coleman CN, Price BD. Increases in sequence specific DNA binding by p53 following treatment with chemotherapeutic and DNA damaging agents. Cancer Res. 1993 May 15;53(10 Suppl):2212–2216. [PubMed]
  • Price BD, Calderwood SK. Increased sequence-specific p53-DNA binding activity after DNA damage is attenuated by phorbol esters. Oncogene. 1993 Nov;8(11):3055–3062. [PubMed]
  • Pagano M, Pepperkok R, Lukas J, Baldin V, Ansorge W, Bartek J, Draetta G. Regulation of the cell cycle by the cdk2 protein kinase in cultured human fibroblasts. J Cell Biol. 1993 Apr;121(1):101–111. [PMC free article] [PubMed]
  • Sherr CJ. G1 phase progression: cycling on cue. Cell. 1994 Nov 18;79(4):551–555. [PubMed]
  • Akiyama T, Ohuchi T, Sumida S, Matsumoto K, Toyoshima K. Phosphorylation of the retinoblastoma protein by cdk2. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7900–7904. [PubMed]
  • Graeber TG, Peterson JF, Tsai M, Monica K, Fornace AJ, Jr, Giaccia AJ. Hypoxia induces accumulation of p53 protein, but activation of a G1-phase checkpoint by low-oxygen conditions is independent of p53 status. Mol Cell Biol. 1994 Sep;14(9):6264–6277. [PMC free article] [PubMed]
  • Jayaraman J, Prives C. Activation of p53 sequence-specific DNA binding by short single strands of DNA requires the p53 C-terminus. Cell. 1995 Jun 30;81(7):1021–1029. [PubMed]
  • Lee S, Elenbaas B, Levine A, Griffith J. p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell. 1995 Jun 30;81(7):1013–1020. [PubMed]
  • Lakdawalla AA, Netrawali MS. Erythrosine, a permitted food dye, is mutagenic in the Bacillus subtilis multigene sporulation assay. Mutat Res. 1988 Oct;206(2):171–176. [PubMed]
  • Lakdawalla AA, Netrawali MS. Mutagenicity, comutagenicity, and antimutagenicity of erythrosine (FD and C red 3), a food dye, in the Ames/Salmonella assay. Mutat Res. 1988 Feb;204(2):131–139. [PubMed]
  • Hiasa Y, Ohshima M, Kitahori Y, Konishi N, Shimoyama T, Sakaguchi Y, Hashimoto H, Minami S, Kato Y. The promoting effects of food dyes, erythrosine (Red 3) and rose bengal B (Red 105), on thyroid tumors in partially thyroidectomized N-bis(2-hydroxypropyl)-nitrosamine-treated rats. Jpn J Cancer Res. 1988 Mar;79(3):314–319. [PubMed]
  • Lippman ME, Dickson RB. Mechanisms of growth control in normal and malignant breast epithelium. Recent Prog Horm Res. 1989;45:383–440. [PubMed]
  • Dees C, Askari M, Foster JS, Ahamed S, Wimalasena J. DDT mimicks estradiol stimulation of breast cancer cells to enter the cell cycle. Mol Carcinog. 1997 Feb;18(2):107–114. [PubMed]
  • Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, et al. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science. 1995 Dec 1;270(5241):1491–1494. [PubMed]
  • Bunone G, Briand PA, Miksicek RJ, Picard D. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J. 1996 May 1;15(9):2174–2183. [PubMed]
  • Joel PB, Traish AM, Lannigan DA. Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Mol Endocrinol. 1995 Aug;9(8):1041–1052. [PubMed]
  • Arnold SF, Klotz DM, Collins BM, Vonier PM, Guillette LJ, Jr, McLachlan JA. Synergistic activation of estrogen receptor with combinations of environmental chemicals. Science. 1996 Jun 7;272(5267):1489–1492. [PubMed]
  • Russo J, Gusterson BA, Rogers AE, Russo IH, Wellings SR, van Zwieten MJ. Comparative study of human and rat mammary tumorigenesis. Lab Invest. 1990 Mar;62(3):244–278. [PubMed]
  • Nelson KG, Sakai Y, Eitzman B, Steed T, McLachlan J. Exposure to diethylstilbestrol during a critical developmental period of the mouse reproductive tract leads to persistent induction of two estrogen-regulated genes. Cell Growth Differ. 1994 Jun;5(6):595–606. [PubMed]

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