Abstract |
We have examined the activities of two novel aza-anthracene-9,10-diones (aza), 1-aza and 2-aza, in HL-60 human leukemia cell lines containing type II topoisomerases with different sensitivities to inhibition by other intercalating agents. The sensitive line, HL-60, was sensitive to 2-aza but not to 1-aza, whereas the resistant HL-60/ AMSA was sensitive to neither agent. Measurements of 1- and 2-aza-induced, topoisomerase II-mediated DNA cross-linking in the cells revealed patterns of resistance and sensitivity that paralleled the results in the cytotoxicity assays. However, measurements of drug-induced topoisomerase II-mediated DNA cross-linking using purified HL-60 and HL-60/ AMSA topoisomerase II indicated that both agents could stabilize a covalent complex between DNA and the HL-60 enzyme. HL-60/ AMSA topoisomerase II resisted stabilization by either agent. This suggests that the resistance of HL-60 cells to 1-aza is not due to the inability of this drug to inhibit topoisomerase II but rather to another, undefined mechanism.
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Authors | L A Zwelling, J Mayes, E Altschuler, P Satitpunwaycha, T R Tritton, M P Hacker |
Journal | Biochemical pharmacology
(Biochem Pharmacol)
Vol. 46
Issue 2
Pg. 265-71
(Jul 20 1993)
ISSN: 0006-2952 [Print] England |
PMID | 8394077
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anthraquinones
- Intercalating Agents
- Isoquinolines
- Quinolones
- Topoisomerase II Inhibitors
- 5,8-bis(2-aminoethylamino)-1-azaanthracene-9,10-dione
- DNA
- DNA Topoisomerases, Type II
- pixantrone
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Topics |
- Anthraquinones
(pharmacology)
- DNA
(metabolism)
- DNA Topoisomerases, Type II
(metabolism)
- Drug Resistance
- Humans
- Intercalating Agents
(pharmacology)
- Isoquinolines
(pharmacology)
- Leukemia
(enzymology)
- Quinolones
- Topoisomerase II Inhibitors
- Tumor Cells, Cultured
(drug effects)
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