Effects of morpholinyl doxorubicins, doxorubicin, and actinomycin D on mammalian DNA topoisomerases I and II.

Abstract:

:The effect of cyanomorpholinyldoxorubicin, morpholinyldoxorubicin, doxorubicin, and Actinomycin D were studied on purified mouse leukemia (L1210) DNA topoisomerases I and II. DNA unwinding and cross-linking were also studied. It was found that 1) morpholinyldoxorubicin, cyanomorpholinyldoxorubicin, and Actinomycin D (but not doxorubicin) stimulated DNA topoisomerase I-induced cleavage at specific DNA sites; 2) only doxorubicin and Actinomycin D stimulated DNA cleavage by DNA topoisomerase II; 3) at higher drug concentrations, DNA intercalators suppressed enzyme-mediated DNA cleavage induced by DNA topoisomerase I, as well as topoisomerase II; 4) only cyanomorpholinyldoxorubicin produced DNA-DNA cross-links; no DNA unwinding could be observed; and 5) DNA intercalation (unwinding) potency of morpholinyldoxorubicin was about 2-fold less than that of doxorubicin. The data indicate that some DNA intercalators are not only inhibitors of DNA topoisomerase II but act also on DNA topoisomerase I. The stabilization of cleavage intermediates by intercalators may have a common mechanism for DNA topoisomerase I and DNA topoisomerase II.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Wassermann K,Markovits J,Jaxel C,Capranico G,Kohn KW,Pommier Y

subject

Has Abstract

pub_date

1990-07-01 00:00:00

pages

38-45

issue

1

eissn

0026-895X

issn

1521-0111

journal_volume

38

pub_type

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