DNA damage induced by bleomycin in the presence of dibucaine is not predictive of cell growth inhibition

David E. Berry, Sidney Hecht, Sidney M. Hecht

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Growth inhibition and cell killing by bleomycin are believed to be related to the ability of this antibiotic to cleave chromosomal DNA. Because bleomycin has an intracellular site of action, its ability to cross biological membranes must be critical to its overall effectiveness as an antitumor agent. The local anesthetic dibucaine acts to enhance membrane fluidity; therefore, the reported ability of this local anesthetic to modulate bleomycin effects on KB cells was investigated. Cells were treated with various oleomycin congeners in the presence or absence of dibucaine for 24 h. Dibucaine enhanced the inhibition of cell growth mediated by bleomycin A2, demethylbleomycin A2, bleomycin B2, and isobleomycin A2. N-Acetyl bleomycin A2 did not inhibit cell growth in the absence of dibucaine, but it was inhibitory in the presence of dibucaine. Cells treated simultaneously for analysis of DNA breakage on alkaline sucrose gradients revealed that breakage was also enhanced in the presence of dibucaine. The degree of enhancement varied with dose and bleomycin congener. N-Acetylbleomycin A2 did not induce DNA breakage in either the absence or the presence of dibucaine. While growth inhibition and net DNA breakage correlated reasonably well in the absence of dibucaine for each bleomycin analogue tested, proportionality was lost in the presence of dibucaine, and very little DNA breakage was present when growth inhibition was complete. These observations imply that, at least in the presence of dibucaine, bleomycin may mediate growth inhibition at some locus in addition to chromosomal DNA and, also, that a given net amount of bleomycin analogue induced DNA damage per se does not produce a specific degree of growth inhibition.

Original languageEnglish (US)
Pages (from-to)3214-3219
Number of pages6
JournalBiochemistry
Volume24
Issue number13
StatePublished - 1985
Externally publishedYes

Fingerprint

Dibucaine
Bleomycin
Cell growth
DNA Damage
DNA
Growth
Local Anesthetics
varespladib methyl
indium-bleomycin
Biological membranes
KB Cells
Membrane Fluidity
Fluidity
Antineoplastic Agents
Sucrose
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

DNA damage induced by bleomycin in the presence of dibucaine is not predictive of cell growth inhibition. / Berry, David E.; Hecht, Sidney; Hecht, Sidney M.

In: Biochemistry, Vol. 24, No. 13, 1985, p. 3214-3219.

Research output: Contribution to journalArticle

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