NUCLEAR TOPOISOMERASE-II ACTIVITY CHANGES DURING HL-60 LEUKEMIC-CELL DIFFERENTIATION - ALTERATIONS IN DRUG SENSITIVITY AND PH DEPENDENCY

被引：6

作者：

GIESELER, F

BOEGE, F

BIERSACK, H

SPOHN, B

CLARK, M

WILMS, K

机构：

[1] Medizinische Poliklinik, University of Wuerzburg

来源：

LEUKEMIA & LYMPHOMA | 1991年 / 5卷 / 04期

关键词：

HL-60; TOPOISOMERASE-II; DIFFERENTIATION; ETOPOSIDE; M-AMSACRINE; DRUG-RESISTANCE;

D O I：

10.3109/10428199109068137

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We have studied the effect of dimethyl-sulfoxide(DMSO)-induced granulocytic differentiation on the sensitivity of HL-60 cells to various cytotoxic topoisomerase II inhibitors: (i) undifferentiated HL-60 cells are highly sensitive to etoposide, while differentiated HL-60 cells are 700-1000 fold resistant to etoposide, (ii) undifferentiated HL-60 are 50-100 fold resistant against 4-(9-acridinylamino)methanesulfon-m-anisidide (mAMSA) when compared to the differentiated HL-60 cells, (iii) the addition of mAMSA to the medium inhibits granulocytic differentiation of HL-60 cells. This change in resistance pattern is probably due to an alteration of topoisomerases since distinctive iso-activites of topoisomerase can be discriminated on the basis of the pH profile, which alters markedly during differentiation. In an etoposide-resistant HL-60 cell line we found a reduced topoisomerase activity at pH 7.8/7.9. This topoisomerase iso-activity is obviously involved in etoposide cytotoxicity. © 1991 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

引用

页码：273 / 279

页数：7

共 13 条

[1]

Kaplan J.G., Brown D.L., Chaly N., Greer W.L., Prasa K.V., Severini A., Sahai B.M., Structural and evolutionary implications if the packaging of DNA for differentiation and proliferation in the lymphocyte, J. Mol. Evol, 26, 3, pp. 172-179, (1987)

[2]

Riou J.F., Multon E., Vilarem M.J., Larsen C.J., Riou G., In vivo stimulation by antitumor drugs of the topoisomerase II induced cleavage sites in c-myc protooncogene, Biochem. Biophys. Res. Comm, 137, pp. 154-160, (1986)

[3]

Darby M.K., Herrera R.E., Vosberg H.P., Nordheim A., DNA topoisomerase II cleaves at specific sites in the 5′ flanking region of c-fos proto-oncogenes in vitro, EMBO J, 5, pp. 2257-2265, (1986)

[4]

Kafiani C.A., Bronstein I.B., Timofeev A.V., Gromova I., Terskikh V., DNA-topoisomerases and regulation of cell proliferation, Adv. Enzyme Regul, 25, pp. 439-457, (1986)

[5]

Osheroff N., Biochemical basis for the interactions of type I and type II topoisomerases with DNA, Pharmacol. Ther, 41, pp. 1-2, (1989)

[6]

Liu L.F., DNA Topoisomerase poisons as antitumor drugs, Ann. Rev. Biochem, 58, pp. 351-375, (1989)

[7]

Zwelling L.A., Silbermann L., Estey E., Intercalator-induced, topoisomerase II-mediated DNA cleavage and its modification by antineoplastic antimetabolites, Int. J. Radiat. Oncol. Biol. Phys, 12, pp. 1041-1047, (1986)

[8]

Deffie A.M., Batra J.K., Goldemberg G.J., Direct correlation between DNA topoisomerase II activity and cytotoxicity in adriamycin-sensitive and -resistant P388 leukemia cell lines, Cancer Res, 49, pp. 58-62, (1989)

[9]

Gieseler F., Meyer P., Schiffmann D., Wilms K., Granulocytic differentiation of HL-60 cells is not regulated by DNS de novo methylation, Blut, 58, pp. 159-163, (1989)

[10]

Meyer P., Epe B., Gieseler F., Topoisomerase II activity influences DMSO induced differentiation in HL-60 cells, Cancer Res. Clin. Oncol, 113, (1987)

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