Diesel exhaust particles (DEPs) cause many adverse health problems, and reports indicate increased risk of
breast cancer in men and women through exposure to
gasoline and vehicle exhaust. However, DEPs include vast numbers of compounds, and the specific compound(s) responsible for these actions are not clear. We recently isolated two
nitrophenols from DEPs-3-methyl-4-nitrophenol (4-nitro-
m-cresol; PNMC) and
4-nitro-3-phenylphenol (PNMPP)-and showed that they had estrogenic and anti-androgenic activities. Here, we tried to clarify the involvement of these two
nitrophenols in promoting the growth of the MCF-7
breast cancer cell line. First, comet assay was used to detect the genotoxicity of PNMC and PNMPP in a CHO cell line. At all doses tested, PNMC and PNMPP showed negative genotoxicity, indicating that they had no
tumor initiating activity. Next, the
estrogen-responsive
breast cancer cell line MCF-7 was used to assess cell proliferation. Proliferation of MCF-7 cells was stimulated by PNMC, PNMPP, and
estradiol-17beta and the anti-
estrogens 4-hydroxytamoxifen and
ICI 182,780 inhibited the proliferation. To further investigate transcriptional activity through the
estrogen receptor, MCF-7 cells were transfected with a receptor gene that allowed expression of
luciferase enzyme under the control of the
estrogen regulatory
element. PNMC and PNMPP induced
luciferase activity in a dose-dependent manner at submicromolar concentrations.
ICI 182,780 inhibited the
luciferase activity induced by PNMC and PNMPP. These results clearly indicate that PNMC and PNMPP do not show genotoxicity but act as
tumor promoters in an
estrogen receptor alpha-predominant
breast cancer cell line.