Two actions of bleomycin on superhelical DNA

Steven L. Ross, Robb Moses

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Bleomycin is an antitumor and antimicrobial drug which appears to exert a direct effect on DNA in vivo. A shift to lower molecular weight as defined by alkaline isokinetic analysis after exposure to bleomycin has been interpreted as indicating that the drug causes single-strand nicks in the DNA. We have used φX174 RFI DNA as a substrate for bleomycin since a single nick in the supercoil produces a marked change in sedimentation properties. We find that bleomycin-treated φX174 DNA sediments through alkaline sucrose in a manner indicating strand breakage. However, we do not observe any change between bleomycin-treated and untreated DNA when sedimentation is done on neutral gradients. This result indicates that bleomycin induces alkaline-sensitive sites in the DNA but does not cause a single-strand break. The alkaline sensitivity of bleomycin-treated DNA is not increased by heating, a different result than with alkylation of DNA. Phosphodiester bond cleavage does occur in neutral conditions if dithiothreitol is added to the incubation mixture. Our results are compatible with removal of a base moiety by bleomycin and with strand scission when dithiothreitol is present.

Original languageEnglish (US)
Pages (from-to)581-586
Number of pages6
JournalBiochemistry
Volume17
Issue number4
StatePublished - 1978
Externally publishedYes

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Superhelical DNA
Bleomycin
DNA
Dithiothreitol
Sedimentation
Single-Stranded DNA Breaks
Alkylation
Pharmaceutical Preparations
Antineoplastic Agents
Heating
Sucrose
Sediments
Molecular Weight
Molecular weight

ASJC Scopus subject areas

  • Biochemistry

Cite this

Two actions of bleomycin on superhelical DNA. / Ross, Steven L.; Moses, Robb.

In: Biochemistry, Vol. 17, No. 4, 1978, p. 581-586.

Research output: Contribution to journalArticle

Ross, SL & Moses, R 1978, 'Two actions of bleomycin on superhelical DNA', Biochemistry, vol. 17, no. 4, pp. 581-586.
Ross, Steven L. ; Moses, Robb. / Two actions of bleomycin on superhelical DNA. In: Biochemistry. 1978 ; Vol. 17, No. 4. pp. 581-586.
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