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4‐Quinolones cause a selective loss of mitochondrial DNA from mouse L1210 leukemia cells
Author(s) -
Lawrence Jeffrey W.,
DarkinRattray Sandra,
Xie Fan,
Neims Allen H.,
Rowe Thomas C.
Publication year - 1993
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240510208
Subject(s) - mitochondrial dna , dna , l1210 cells , chemistry , leukemia , cancer research , biology , microbiology and biotechnology , genetics , gene , biochemistry , cytotoxicity , in vitro
The 4‐quinolone antibiotics nalidixic acid and ciprofloxacin and potent inhibitors of the bacterial type II topoisomerase DNA gyrase. Treatment of mouse L1210 leukemia cells with these drugs resulted in a delayed inhibition of cell proliferation. Prior to inhibition of cell proliferation, there was a time‐dependent decrease in the cellular content of mitochondrial DNA (mtDNA). The decrease in mtDNA was associated with a decrease in the rate of mitochondrial respiration and an increase in the concentration of lactate in the growth medium. Inhibition of cell proliferation by 4‐quinolones was reversible upon drug washout. However, there was a 2‐ to 4‐day lag before the growth rate returned to normal levels. This was preceeded by an increase in mtDNA content and mitochondrial respiration. These studies suggest that inhibition of mammalian cell proliferation by 4‐quinolone drugs is related to the selective depletion of mtDNA. © 1993 Wiley‐Liss, Inc.