Similarities Between Acetaminophen- and Estradiol-Induced Proliferation of Cultured, Estrogen-Responsive Breast Cancer Cells

Details

• Personal Author:
  Harnagea-Theophilus E ; Miller MR
• Description:
  Studies in this laboratory have shown that acetaminophen, a widely used analgesic/antipyretic, induces DNA synthesis and proliferation in estrogen responsive (ER +) but not estrogen-nonresponsive (ER-) cultured. human breast cancer cells. Like estradiol, acetaminophen contains a p-phenol moiety; this moiety appears to influence estradiol- and xenoestrogen-induced ER+ cell proliferation. Thus, the first goal of this research was to determine the importance of the p-phenol moiety in acetaminophen-induced proliferation. To this end, effects of p-, m-, and o-acetamidophenol on ER+ (MCF7 and T47D) cell proliferation and on % cells in S (DNA synthesis) phase of the cell cycle were determined. Therapeutic concentrations of p-acetamidophenol (- 0.1 mM) significantly increased proliferation, and the relative order of potency was p- greater than m. greater than o-acetamidophenol. These data suggest the p-phenol moiety is important in both estradiol- and acetaminophen-induced ER+ cell proliferation. The second goal of this research was to establish if estrogen receptor pathways are involved in mediating the acetaminophen induced proliferation of ER+ cells. Two antiestrogens (ICI 182,780 and 4 hydroxytamoxifen) were tested in 2 ER+ (MCF7, T47D) and 1 estrogennonresponsive, ER- (MDA-MB-231) cell lines. Effects of antiestrogens on acetaminophen-induced proliferation were assessed by flow cytometry (0/0 S phase cells) and by cell counting. In MCF7 and 1470 cells (but not in MDA MB-231 cells), both antiestrogens inhibited proliferation induced by acetaminophen and by estradiol. These data also suggest that there are similarities between estradiol- and acetaminophen-induced proliferation. Furthermore, estrogen receptors may directly or indirectly mediate the acetaminophen induced proliferation of ER+ cells. [Description provided by NIOSH]
• Subjects:
  Carcinogens Cells, Cultured Chemistry Chemistry, Analytic Environmental Monitoring Estrogens Hazardous Substances Neoplasms Occupational Health Safety Toxicology

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• Keywords:
  Analgesics Analytical-chemistry Analytical-methods Breast-cancer Cancer Carcinogenesis Cell-cultures Cell-function Cellular-function Cellular-structures Estrogenic-hormones Exposure-assessment Statistical-analysis Toxic-materials Toxins

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  379-380
• Volume:
  48
• NIOSHTIC Number:
  nn:20027990
• Citation:
  Toxicologist 1999 Mar; 48(1-S):379-380
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana
• Supplement:
  1-S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c102b64bcc8b3cdb46ec25cce7667f6a80dabf2aa365a734afecb712552e4f6df21cbaf30b7ca1aaeaa54e08e01abf9c924e6a92d58ae359414ad2f3c8873e0c
• Download URL:
  https://stacks.cdc.gov/view/cdc/189718/cdc_189718_DS1.pdf
• File Type:
  [PDF - 259.63 KB ]