Increased Oxidative DNA Damage in Mammary Tumor Cells by Continuous Epidermal Growth Factor Stimulation: p. 166

• Published in: JNCI : Journal of the National Cancer Institute 2001-02, Vol.93 (3), p.214
• Main Authors: Hamada, Jun-ichi, Nakata, Daichi, Nakae, Dai, Kobayashi, Yozo, Akai, Hiroyuki, Konishi, Yoichi, Okada, Futoshi, Shibata, Toshiyuki, Hosokawa, Masuo, Moriuchi, Tetsuya
• Format: Article
• Language: English
• ISSN: 0027-8874; 1460-2105

Background: Growth factors can enhance the malignant potential of tumor cells. To examine the relationship between growth factors and tumor progression, we previously established a weakly malignant cell line, ER-1. We found that a 24-hour exposure of ER-1 cells to epidermal growth factor (EGF) induced malignant properties (tumor progression) that were reversible but that, after a 1-month exposure, these changes were irreversible. In this study, we investigated the irreversible changes induced in ER-1 cells by a 1-month exposure to EGF and the possible involvement of oxidative stress. Methods: ER-1 cells were treated with EGF (100 ng/mL) for 1 month in the presence or absence of an antioxidant, N-acetylcysteine or selenium, and compared with untreated control ER-1 cells. We assessed tumor progression by measuring intracellular peroxide levels, 8-hydroxydeoxyguanosine (a marker for oxidative DNA damage) levels, in vitro invasiveness, and in vivo tumorigenicity and metastatic ability. All statistical tests are two-sided. Results: After ER-1 cells were treated for 1 month with EGF, levels of intracellular peroxide and 8-hydroxyguanosine in the DNA of treated cells were higher than those in the DNA of control cells, and treated ER-1 cells were more tumorigenic and metastatic in vivo and more invasive in vitro than untreated control cells (all P