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Copper chelator enhancement of bleomycin cytotoxicity
Author(s) -
Lin P. S.,
Kwock L.,
Goodchild N. T.
Publication year - 1980
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19801201)46:11<2360::aid-cncr2820461108>3.0.co;2-a
Subject(s) - bleomycin , cytotoxicity , superoxide dismutase , superoxide , hydrogen peroxide , clonogenic assay , chinese hamster , radical , hydroxyl radical , biochemistry , reactive oxygen species , chelation , chemistry , in vitro , microbiology and biotechnology , medicine , biology , enzyme , chemotherapy , organic chemistry
Bleomycin's effects on DNA strand scission are inhibited by low concentration of some metal ions (including copper), greatly stimulated by ferrous (Fe +2 ) ions, and increased and probably mediated by the production of superoxide radicals (O 2 ‐ ), hydroxyl radicals (OH), and hydrogen peroxide (H 2 O 2 ). However, the role of these mechanisms in overall bleomycin cytotoxicity is not known. For this reason, we have treated the Chinese hamster cell line (V79) cells with a copper chelator, diethyldithiocarbamate (DDC) and bleomycin in vitro DDC is known to inhibit superoxide dismutase (SOD), an enzyme responsible for the scavenging of O 2 ‐ . The cytotoxicity is determined by the standard clonogenic survival method, which shows that DDC treated cells are more susceptible to bleomycin either as a function of bleomycin dose or as a function of bleomycin treatment time. These results support the notion that reducing Cu 2+ levels and/or increasing O 2 ‐ concentrations can modify the cytotoxicity of bleomycin.