DNA damage by antitumor acridines mediated by mammalian DNA topoisomerase II

T. C. Rowe, G. L. Chen, Y. H. Hsiang, Leroy-Fong Liu

Research output: Contribution to journalArticle

235 Citations (Scopus)

Abstract

Antitumor drugs from many chemical classes have been shown to induce protein-linked DNA breaks in cultured mammalian cells and in vitro in the presence of purified mammalian DNA topoisomerase II. The possibility that mammalian DNA topoisomerase II is an intracellular target which mediates drug-induced DNA breaks is supported by the following studies using 4'-(9-acridinylamino)methane-sulfon-m-anisidide (m-AMSA): (a) a single m-AMSA-dependent DNA cleavage activity copurified with calf thymus DNA topoisomerase II activity at all chromatographic steps of the enzyme purification; (b) m-AMSA-induced DNA cleavage by this purified activity resulted in the covalent attachment of protein to the 5'-ends of the DNA via a tyrosyl phosphate bond. This covalently linked protein has the same reduced molecular weight as purified calf thymus DNA topoisomerase II. The possibility that topoisomerase II-mediated DNA breaks may be responsible for cytotoxicity has also been investigated using a number of m-AMSA-related acridines. The level of topoisomerase II-mediated DNA breaks in vitro strongly correlates with the level of protein-linked DNA breaks in cultured cells and drug-induced cytotoxicity. These results suggest that mammalian DNA topoisomerase II may be a cytotoxic target of antitumor acridines.

Original languageEnglish
Pages (from-to)2021-2026
Number of pages6
JournalCancer Research
Volume46
Issue number4 II
Publication statusPublished - 1986
Externally publishedYes

Fingerprint

Acridines
Type II DNA Topoisomerase
DNA Damage
DNA Breaks
Amsacrine
DNA Cleavage
Cultured Cells
Proteins
Methane
Pharmaceutical Preparations
Antineoplastic Agents
Molecular Weight
Phosphates
DNA
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rowe, T. C., Chen, G. L., Hsiang, Y. H., & Liu, L-F. (1986). DNA damage by antitumor acridines mediated by mammalian DNA topoisomerase II. Cancer Research, 46(4 II), 2021-2026.

DNA damage by antitumor acridines mediated by mammalian DNA topoisomerase II. / Rowe, T. C.; Chen, G. L.; Hsiang, Y. H.; Liu, Leroy-Fong.

In: Cancer Research, Vol. 46, No. 4 II, 1986, p. 2021-2026.

Research output: Contribution to journalArticle

Rowe, TC, Chen, GL, Hsiang, YH & Liu, L-F 1986, 'DNA damage by antitumor acridines mediated by mammalian DNA topoisomerase II', Cancer Research, vol. 46, no. 4 II, pp. 2021-2026.
Rowe, T. C. ; Chen, G. L. ; Hsiang, Y. H. ; Liu, Leroy-Fong. / DNA damage by antitumor acridines mediated by mammalian DNA topoisomerase II. In: Cancer Research. 1986 ; Vol. 46, No. 4 II. pp. 2021-2026.
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