V79 Chinese hamster lung cells resistant to the bis-alkylator bizelesin are multidrug-resistant.

Abstract:

:Bizelesin (U-77779) is a highly potent bis-alkylating antitumor agent that is effective against several tumor systems in vitro and in vivo. V79 cells that were 125- to 250-fold resistant to bizelesin developed after constant exposure to gradually increasing concentrations of the drug. Resistant cells exhibited a multidrug-resistant phenotype and genotype as indicated by cross-resistant to several structurally and functionally unrelated drugs, e.g., colchicine, actinomycin D, and Adriamycin, and overexpression of mdr mRNA. Very low levels of cross-resistance to the alkylating agents cisplatin and melphalan were seen. Multidrug-resistant mouse leukemia (P388/Adriamycin-resistant) and human (KB/vinblastine-resistant) cells were also resistant to bizelesin. Bizelesin resistance was unstable and decreased when cells were grown in the absence of the drug. Resistant and sensitive cell lines had similar levels of glutathione, and bizelesin cytotoxicity for resistant cells was not markedly affected by treatment with buthionine sulfoximine. Cross-resistance between bizelesin and several of its analogs is reported.

authors

Butryn RK,Smith KS,Adams EG,Abraham I,Stackpole J,Sampson KE,Bhuyan BK

doi

10.1007/BF00686110

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

44-50

issue

1

eissn

0344-5704

issn

1432-0843

journal_volume

34

pub_type

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