Abstract
The bleomycins (BLMs) are a family of antitumor antibiotics used clinically for the treatment of squamous cell carcinomas and malignant lymphomas (1–4). Bleomycin A2 is the major constituent of the clinically used mixture of bleomycins. Although biochemical studies have indicated several loci that may contribute to the overall therapeutic effects obtained with bleomycin, the accumulated evidence suggests that the primary effect is at the level of oxidative DNA degradation (5). DNA degradation mediated by bleomycin is metal ion dependent; with the exception of Co·BLM (6), DNA degradation by metallobleomycins also requires oxygen (5,7). It is believed that the degradative event is actually mediated by a ternary complex consisting of bleomycin, a metal ion and oxygen. There are several mechanistically interesting facets of BLM-mediated DNA degradation, including the observed sequence selectivity for 5’-GT-3’ sequences (7–9) and the fact that double-strand cleavage occurs at a frequency greater than that expected from the random accumulation of single-strand breaks (10,11).
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References
S. K. Carter, The current role of bleomycin in cancer therapy. In: Bleomycin: Current Status and New Developments (S. K. Carter; S. T. Crooke; H. Umezawa, Eds.), pp. 9–14. Academic Press, New York, 1978.
S. M. Hecht, Summary of the bleomycin symposium. In Bleomycin: Chemical. Biochemical and Biological Aspects (S.M. Hecht, Ed.) pp. 1–23. Springer-Verlag, New York, 1979.
H. Umezawa, Recent studies on biochemistry and action of bleomycin. In: Bleomycin: Current Status and New Developments (S. K. Carter; S. T. Crooke; H. Umezawa, Eds.), pp. 15–19. Academic Press, New York, 1978.
H. Umezawa, Recent studies on bleomycin. Lloydia, 40, 67–81 (1977).
S. M. Hecht, DNA strand scission by activated bleomycin group antibiotics. Fed. Proc. 45. 2784–2791 (1986).
L.-H. Chang and C.F. Meares, Cobalt-bleomycins and deoxyribonucleic acid: sequence-dependent interactions, action spectrum for nicking, and indifference to oxygen. Biochemistry 23, 2268–2274 (1984).
A. D. D’Andrea and W.A. Haseltine, Sequence specific cleavage of DNA by the antitumor antibiotics neocarzinostatin and bleomycin. Proc. Natl. Acad. Sci. U.S.A. 75, 3608–3612 (1978).
M. Takeshita, A. Grollman; E. Ohtsubo and H. Ohtsubo, Interaction of bleomycin with DNA. Proc. Natl. Acad. Sci. U.S.A. 75, 5983–5987 (1978).
C. K. Mirabelli, A. Ting, C.-H. Huang, S. Mong, and S. T. Crooke, Bleomycin and talisomycin sequence-specific strand scission of DNA: A mechanism of double-strand cleavage. Cancer Res. 42, 2779–2785 (1982).
C. W. Haidle, R. S. Lloyd and D. L. Robberson. Molecular aspects of bleomycin-promoted damage of covalently closed circular DNA. In: Bleomycin: Chemical, Biochemical, and Biological Aspects; (S. M. Hecht, Ed.) pp. 222–243. Springer-Verlag, New York, 1979.
C.-H. Huang, C. K. Mirabelli, Y. Jan, and S. T. Crooke, Single-strand and double-strand deoxyribonucleic acid breaks produced by several bleomycin analogues. Biochemistry 20, 233–238 (1981).
L. Giloni, M. Takeshita, F. Johnson, C. Iden, and A. P. Grollman, Bleomycin-induced strand scission of DNA, J. Biol. Chem. 256, 8608–8615 (1981).
N. Murugesan, C. Xu, G. M. Ehrenfeld, H. Sugiyama, R. E. Kilkuskie, L. O. Rodriguez, L.-H. Chang, and S. M. Hecht, Analysis of products formed during bleomycin-mediated DNA degradation. Biochemistry 24, 5735–5744 (1985).
H. Sugiyama, C. Xu, N. Murugesan, and S.M. Hecht, Structure of the alkali-labile product formed during iron(II)-bleomycin-mediated DNA strand scission. J. Am. Chem. Soc. 107, 4104–4105 (1985).
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© 1987 Plenum Press, New York
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Hecht, S.M. (1987). DNA Strand Scission by Activated Bleomycin Group Antibiotics. In: Cerutti, P.A., Nygaard, O.F., Simic, M.G. (eds) Anticarcinogenesis and Radiation Protection. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6462-1_65
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DOI: https://doi.org/10.1007/978-1-4615-6462-1_65
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