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Similarities between acetaminophen- and estradiol-induced proliferation of cultured, estrogen-responsive breast cancer cells.
Toxicologist 1999 Mar; 48(1-S):379-380
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.
Statistical-analysis; Analytical-methods; Analytical-chemistry; Exposure-assessment; Toxicology; Toxins; Toxic-materials; Estrogenic-hormones; Analgesics; Cell-cultures; Cell-function; Cellular-function; Cellular-structures; Breast-cancer; Cancer; Carcinogens; Carcinogenesis
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana