Potentiation of bleomycin cytotoxicity in Saccharomyces cerevisiae.

Antimicrobial Agents and Chemotherapy
C W Moore

Abstract

Lesions introduced into cellular DNAs prelabeled with [2-14C]thymidine or [6-3H]thymidine, as well as cell killing, were inhibited by the presence of EDTA during 20-min reactions of Saccharomyces cerevisiae cells with the low-molecular-weight bleomycin family of anticancer antibiotics. In contrast, the level of killing by low concentrations of bleomycin was higher among cells which had grown for three generations in defined synthetic complete medium supplemented with ferrous sulfate than among cells grown without iron supplementation. In S. cerevisiae, the uptake of iron is facilitated by a plasma membrane ferric reductase activity and a high-affinity (Km = 5 x 10(-6) M) ferrous uptake system. Lethal effects of 1.3 x 10(-6) M bleomycin increased approximately 50% with 10(-5) M Fe(II), nearly twofold with 10(-4) M Fe(II), and 2.8 times with 10(-3) M Fe(II). Thus, iron preloading is a new experimental approach to increasing and studying the effects of the glycopeptides on cellular DNAs and other cellular targets. This approach could also be used for studying and better understanding DNA repair genes and could serve as a model for studies of redox active chemicals in biological systems.

References

Jul 1, 1976·Cell·M A Forte, W L Fangman
Jul 11, 1978·Biochemistry·E A SausvilleS B Horwitz
Jan 16, 1976·Molecular & General Genetics : MGG·M A Resnick, P Martin
Jan 1, 1990·Chemico-biological Interactions·D H PeteringW E Antholine
Mar 1, 1991·Mutation Research·L F Povirk, M J Austin
May 1, 1988·The Journal of Antibiotics·M Nakamura, J Peisach
Sep 1, 1989·Antimicrobial Agents and Chemotherapy·C W MooreL A Wall
Nov 1, 1987·Journal of General Microbiology·E LesuisseR R Crichton
May 1, 1972·Proceedings of the National Academy of Sciences of the United States of America·T D Petes, W L Fangman
Oct 1, 1971·Analytical Biochemistry·W L Carrier, R B Setlow
May 1, 1967·Journal of Bacteriology·L H Hartwell
Jan 1, 1980·Advances in Enzyme Regulation·A P Grollman, M Takeshita
Feb 16, 1981·Life Sciences·R M BurgerS B Horwitz
Dec 1, 1981·Journal of Inorganic Biochemistry·J M Gutteridge, D J Shute
Jun 1, 1982·Journal of Bioenergetics and Biomembranes·F L CraneH Löw

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Citations

Mar 1, 1996·Antimicrobial Agents and Chemotherapy·J R GraybillM G Rinaldi

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