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The Presence of Single Nucleotide Instability in Human Breast Cancer Cell Lines¹

Carcinogenesis Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045 [N. W., E. O., T. S., T. U.], and Division of Organic and Bio-organic Chemistry, Kyoritsu College of Pharmacy, Shiba-koen 1-5-30, Minato-ku, Tokyo 105-8512 [N. W., M. M.], Japan

The presence of single nucleotide instability, an increase of spontaneous point mutation rates (MR: number of mutations per cell division) without microsatellite instability, was demonstrated previously in two rat mammary carcinoma cell lines. In this study, spontaneous point MRs were analyzed in human breast cancer cell lines by the fluctuation test using the hypoxanthine-guanine phosphoribosyltransferase (hprt) marker gene. MRs obtained for six breast cancer cell lines, MCF-7, ZR-75-1, T-47D, MDA-MB-231, MDA-MB-468, and BT-474, all of which were proficient in G/T mismatch binding and reported to be negative for microsatellite instability, were 7.6, 4.6, 6.3, 2.2, 5.6, and 19 x 10^-7 mutations/hprt/cell division. Those in normal human mammary epithelial cells and in a colon cancer cell line with proficient mismatch repair, SW480, were 1.6 and 1.4 x 10^-7 mutations/hprt/cell division, respectively. These findings showed that single nucleotide instability was also present in five of the six human breast cancer cell lines and strongly indicates it has important roles in human and rat mammary carcinogenesis.

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