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Science 3 July 1964:
Vol. 145. no. 3627, pp. 55 - 58
DOI: 10.1126/science.145.3627.55
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Articles

Mitomycins and Porfiromycin: Chemical Mechanism of Activation and Cross-linking of DNA

V. N. Iyer 1 and Waclaw Szybalski 2

1 Microbiology Research Institute, Canada Department of Agriculture, Ottawa
2 McArdle Memorial Laboratory, University of Wisconsin, Madison

Mitomycins and porfiromycin, generally nonreactive in the natural oxidized state, behave as bifunctional "alkylating" agents upon chemical or enzymatic reduction, followed by spontaneous loss of the tertiary methoxy (hydroxyl) group and formation of an aromatic indole system. Thus activated, mitomycins and porfiromycin react in vitro with purified DNA, linking its complementary strands. A high content of guanine and cytosine favors this cross-linking reaction, which is the basis of the lethal effect in vivo of these antibiotics. The activation and cross-linking reactions are discussed in terms of reactive sites on the mitomycin and DNA molecules.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Mitomycin resistance in mammalian cells expressing the bacterial mitomycin C resistance protein MCRA.
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Mitomycin Resistance in Streptomyces lavendulae Includes a Novel Drug-Binding-Protein-Dependent Export System.
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Bioactivation as a model for drug design bioreductive alkylation.
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Science 197, 527-532
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Molecular Mechanisms of Antibiotic Action.
W. CARTER and K. S. MCCARTY (1966)
Ann Intern Med 64, 1087-1113
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Phenethyl Alcohol Synergism with Mitomycin C, Porfiromycin, and Streptonigrin.
J. R. White and H. L. White (1964)
Science 145, 1312-1313
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Chemical Reactivity of Chromosomal DNA as Related to Mutagenicity: Studies with Human Cell Lines.
W. Szybalski (1964)
Cold Spring Harb Symp Quant Biol 29, 151-159
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Science. ISSN 0036-8075 (print), 1095-9203 (online)