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PMID: 2823270 Published · ppublish English Journal Article

Elevated DNA topoisomerase II activity in nitrogen mustard-resistant human cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 84 ·No. 21 ·1987-11-00 ·Pages 7668-71

Tan KB, Mattern MR, Boyce RA, Schein PS

Abstract

A human Burkitt lymphoma cell line, Raji-HN2, made 10-fold more resistant to nitrogen mustard (HN2) than the parental Raji cell line, exhibited the following characteristics when compared to the parental Raji cells: (i) decreased HN2-induced DNA interstrand crosslinking; (ii) increased (3-fold) DNA topoisomerase II [DNA topoisomerase (ATP-hydrolyzing), EC 5.99.1.3] activity; (iii) increased (4- to 11-fold) sensitivity to topoisomerase II inhibitors; (iv) increased (2-fold) glutathione content; and (v) increased (2-fold) cell doubling time. The resistant phenotype was unstable and was maintained by weekly treatment of the cells with HN2. Growing the resistant cells in the absence of HN2 resulted in a time-dependent decrease in both resistance to HN2 and topoisomerase II activity and an increase in DNA interstrand crosslinking induced by HN2. We hypothesize that HN2 resistance is due to enhanced monoadduct repair with resultant decreased DNA crosslinking and that this process is mediated by topoisomerase II.

MeSH Terms
Antineoplastic Agents/pharmacology Burkitt Lymphoma/enzymology Cell Line DNA Repair DNA Topoisomerases, Type II/metabolism Drug Resistance Glutathione/metabolism Humans Kinetics Mechlorethamine/pharmacology
Chemicals
Antineoplastic Agents Mechlorethamine DNA Topoisomerases, Type II Glutathione
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Tan K B
Department of Molecular Pharmacology, Smith Kline & French Laboratories, Philadelphia, PA 19101.
Mattern M R
Boyce R A
Schein P S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.84.21.7668
Published
1987-11-00
Pages
7668-71
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC299361
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.84.21.7668 PMC Full Text View journal details
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