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Abstrakt
A DNA cross-link adduct of the antitumor agent mitomycin C (MC) to DNA has been isolated and characterized; the results provide direct proof for bifunctional alkylation of DNA by MC. Exposure of MC to Micrococcus luteus DNA under reductive conditions and subsequent nuclease digestion yielded adducts formed between MC and deoxyguanosine residues. In addition to the two known monoadducts, a bisadduct was obtained. Reductive MC activation with Na 2S2O4 (sodium dithionite) leads to exclusive bifunctional alkylation. The structure of the bisadduct was determined by spectroscopic methods that included proton magnetic resonance, differential Fourier transform infrared spectroscopy, and circular dichroism. Formation of the same bisadduct in vivo was demonstrated upon injection of rats with MC. Computer-generated models of the bisadduct that was incorporated into the center of the duplex B-DNA decamer d(CGTACGTACG)2 indicated that the bisadduct fit snugly into the minor groove with minimal distortion of DNA structure. A mechanistic analysis of the factors that govern monofunctional and bifunctional adduct formation is presented.
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Autorzy (6)
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Maria Tomasz
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Roselyn Lipman
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Dondapati Chowdary
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Gregory L. Verdine
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Koji Nakanishi
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Informacje szczegółowe
- Kategoria:
- Publikacja w czasopiśmie
- Typ:
- artykuły w czasopismach
- Opublikowano w:
-
SCIENCE
nr 235,
strony 1204 - 1208,
ISSN: 0036-8075 - Język:
- polski
- Rok wydania:
- 1987
- Opis bibliograficzny:
- Tomasz M., Lipman R., Chowdary D., Pawlak J., Verdine G. L., Nakanishi K.: Isolation and structure of a covalent cross-link adduct between mitomycin C and DNA// SCIENCE -Vol. 235,iss. 4793 (1987), s.1204-1208
- DOI:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1126/science.3103215
- Źródła finansowania:
-
- Publikacja bezkosztowa
- Weryfikacja:
- Politechnika Gdańska
wyświetlono 153 razy
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