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Alkylating agent resistance: in vitro studies with human cell lines.

Abstract：

:Development of in vitro resistance to HN2 (also called mustargen or mechlorethamine hydrochloride), N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), and cisplatin [cis-diamminedichloroplatinum(II)] was achieved in two human cell lines, the Raji/Burkitt lymphoma and a squamous cell carcinoma of the tongue. A 10- to 20-fold increase in resistance relative to the parental line was achieved in 3-4 months of continuous selection pressure. At this time, further increase in selection pressure resulted in cell death, while removal of drug led to rapid loss of resistance. However, by holding selection pressure constant over 8-12 months, semistable clones ranging in resistance up to 8- to 12-fold were obtained. The half-life for resistance loss upon removal of drug was 2-3 months. In the presence of intermittent low concentrations of the alkylating agent, resistance has been maintained in excess of 9 months. With one exception, the growth kinetics of the resistant clones were slightly slower than those of the parental lines. Cross-resistance studies were performed against HN2, BCNU, cisplatin, phenylalanine mustard, and hydroperoxycyclophosphamide. There was, in general, a lack of cross-resistance. We conclude that stable resistance to alkylating agents is produced with difficulty. We propose that these semistable cloned human tumor lines represent clinically relevant models for the study of alkylating agent resistance and that the cross-resistance patterns among these cells have important therapeutic and mechanistic implications.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Frei E 3rd,Cucchi CA,Rosowsky A,Tantravahi R,Bernal S,Ervin TJ,Ruprecht RM,Haseltine WA

doi

10.1073/pnas.82.7.2158

subject

Has Abstract

pub_date

1985-04-01 00:00:00

pages

2158-62

issue

7

eissn

0027-8424

issn

1091-6490

journal_volume

82

pub_type

杂志文章

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