This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pommier, Y. Articles by Bradley, M. O. Search for Related Content PubMed PubMed Citation Articles by Pommier, Y. Articles by Bradley, M. O.

Correlations between Intercalator-induced DNA Strand Breaks and Sister Chromatid Exchanges, Mutations, and Cytotoxicity in Chinese Hamster Cells

Laboratory of Molecular Pharmacology, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, Maryland 20205

Intercalator-induced DNA strand breaks in mammalian cells represent topoisomerase II:DNA complexes trapped by intercalators. These complexes are detected as protein-associated DNA single-strand breaks (SSB) and DNA double-strand breaks (DSB) by filter elution. Using Chinese hamster lung fibroblasts (V79 cells) that were treated for 30 min with various concentrations of 4'-(9-acridinylamino)methanesulfon-m-anisidide or 5-iminodaunorubicin, we measured DNA strand breaks (SSB and DSB), sister chromatid exchanges (SCE), mutations at the hypoxanthine:guanine phosphoribosyltransferase locus, and cell killing. Further, we correlated DNA strand breakage with the three other parameters. Both drugs induced SCE, mutations, and cell killing at concentrations which also produced reversible DNA strand breaks. While the quantity of DSB correlated with SCE, mutations, and cytotoxicity for both drugs, we found more SCE, mutations, and cytotoxicity per SSB in cells treated with 5-iminodaunorubicin than in those treated with 4'-(9-acridinylamino)methanesulfon-m-anisidide. These data show that the DSB (but not the SSB) induced by 4'-(9-acridinylamino)methanesulfon-m-anisidide and 5-iminodaunorubicin at DNA topoisomerase II binding sites correlated closely with SCE, mutations, and cell killing and could therefore be responsible for their production.

¹ To whom requests for reprints should be addressed, at Building 37, Room 5A19, National Cancer Institute, Division of Cancer Treatment, NIH, 9000 Rockville Pike, Bethesda, MD 20205.

² Present address: Department of Chemotherapy Research and Medical Oncology, Division of Medicine, M. D. Anderson Hospital and Tumor Institute, 6723 Bertner Avenue, Houston, TX 77030.

³ Present address: Cytogenetic Oncology Section, Medicine Branch, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, MD 20205.

⁴ Present address: Merck Institute for Therapeutic Research, West Point, PA 19486.

Received 1/ 7/85. Revised 3/19/85. Accepted 4/10/85.

This article has been cited by other articles:

				M. G. Manjanatha, S. Shelton, M. E. Bishop, L. E. Lyn-Cook, and A. Aidoo Dietary effects of soy isoflavones daidzein and genistein on 7,12-dimethylbenz[a]anthracene-induced mammary mutagenesis and carcinogenesis in ovariectomized Big Blue(R) transgenic rats. Carcinogenesis, December 1, 2006; 27(12): 2555 - 2564. [Abstract] [Full Text] [PDF]

				M. Manjanatha, S. Shelton, M. Bishop, L. Lyn-Cook, and A. Aidoo Dietary effects of soy isoflavones daidzein and genistein on 7,12-dimethylbenz[a]anthracene-induced mammary mutagenesis and carcinogenesis in ovariectomized Big Blue transgenic rats Carcinogenesis, October 1, 2006; 27(10): 1970 - 1979. [Abstract] [Full Text] [PDF]

				P. L. Strissel, R. Strick, R. J. Tomek, B. A. Roe, J. D. Rowley, and N. J. Zeleznik-Le DNA structural properties of AF9 are similar to MLL and could act as recombination hot spots resulting in MLL/AF9 translocations and leukemogenesis Hum. Mol. Genet., July 1, 2000; 9(11): 1671 - 1679. [Abstract] [Full Text] [PDF]

				M. Binaschi, R. Farinosi, M. E. Borgnetto, and G. Capranico In Vivo Site Specificity and Human Isoenzyme Selectivity of Two Topoisomerase II-poisoning Anthracyclines Cancer Res., July 1, 2000; 60(14): 3770 - 3776. [Abstract] [Full Text]

				F. Errington, E. Willmore, M. J. Tilby, L. Li, G. Li, W. Li, B. C. Baguley, and C. A. Austin Murine Transgenic Cells Lacking DNA Topoisomerase IIbeta Are Resistant to Acridines and Mitoxantrone: Analysis of Cytotoxicity and Cleavable Complex Formation Mol. Pharmacol., December 1, 1999; 56(6): 1309 - 1316. [Abstract] [Full Text]

				K. Tanaka, M. Arif, M. Eguchi, T. Kyo, H. Dohy, and N. Kamada Frequent Jumping Translocations of Chromosomal Segments Involving the ABL Oncogene Alone or in Combination With CD3-MLL Genes in Secondary Leukemias Blood, January 15, 1997; 89(2): 596 - 600. [Abstract] [Full Text] [PDF]

				M Morse-Gaudio and M. Risley Topoisomerase II expression and VM-26 induction of DNA breaks during spermatogenesis in Xenopus laevis J. Cell Sci., January 10, 1994; 107(10): 2887 - 2898. [Abstract] [PDF]