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The effect of BCNU and adriamycin on normal and G6PD deficient erythrocytes
Author(s) -
Sagone Arthur L.,
Burton G. Mark
Publication year - 1979
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830070202
Subject(s) - glutathione , chemistry , pentose phosphate pathway , hydrogen peroxide , glutathione reductase , biochemistry , stimulation , red blood cell , oxidative stress , pharmacology , carmustine , enzyme , chemotherapy , medicine , endocrinology , biology , glutathione peroxidase , cyclophosphamide , glycolysis
In cell free systems Adriamycin induces oxygen radicals. We have shown previously that Adriamycin generates peroxide in human erythrocytes. BCNU, by inhibiting glutathione reductase, interferes with the major erythrocyte pathway to degrade peroxide. In this investigation we looked at interactions of these drugs with normal and abnormal erythrocytes. In G6PD‐deficient erythrocytes Adriamycin posed a significant oxidant stress as demonstrated by hexose monophosphate shunt (HMPS) activity, hydrogen peroxide (H 2 O 2 ) production, and glutathione depletion. At similar molar concentrations Adriamycin was a stronger oxidant than acetylphenylhydrazine. BCNU‐treated normal erythrocytes showed an enhanced susceptibility to oxidant stress as demonstrated by a lack of HMPS response to H 2 O 2 and glutathione depletion during incubations with Adriamycin. The HMPS shunt of BCNU treated RBC was intact as shown by their nearly normal response to methylene blue stimulation. These BCNU studies also demonstrated the inability of H 2 O 2 to react directly with NADPH. In conclusion Adriamycin poses a potent oxident stress to G6PD‐deficient erythrocytes. BCNU promotes enhanced susceptibility of normal RBC to oxidant stress and BCNU can act as a probe to define drug interactions with the HMPS. These studies add to a growing body of evidence postulating the importance of oxygen radicals in the therapeutic and/or effects of Adriamycin.