Biomaterial Database

The effect of BCNU and adriamycin on normal and G6PD deficient erythrocytes. 1979

A L Sagone, and G M Burton

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 (H2O2) 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 H2O2 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 H2O2 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.

UI	MeSH Term	Description	Entries
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D002330	Carmustine	A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)	BCNU,1,3-Bis(2-Chloroethyl)-1-Nitrosourea,BiCNU,FIVB,N,N'-Bis(2-Chloroethyl)-N-Nitrosourea,Nitrumon
D004317	Doxorubicin	Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.	Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D004912	Erythrocytes	Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.	Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D005561	Formates	Derivatives of formic acids. Included under this heading are a broad variety of acid forms, salts, esters, and amides that are formed with a single carbon carboxy group.	Formic Acids,Acids, Formic
D005955	Glucosephosphate Dehydrogenase Deficiency	A disease-producing enzyme deficiency subject to many variants, some of which cause a deficiency of GLUCOSE-6-PHOSPHATE DEHYDROGENASE activity in erythrocytes, leading to hemolytic anemia.	Deficiency of Glucose-6-Phosphate Dehydrogenase,Deficiency, GPD,Deficiency, Glucosephosphate Dehydrogenase,G6PD Deficiency,GPD Deficiency,Glucose 6 Phosphate Dehydrogenase Deficiency,Glucose-6-Phosphate Dehydrogenase Deficiency,Glucosephosphate Dehydrogenase Deficiencies,Hemolytic Anemia Due to G6PD Deficiency,Deficiencies, G6PD,Deficiencies, GPD,Deficiencies, Glucose-6-Phosphate Dehydrogenase,Deficiencies, Glucosephosphate Dehydrogenase,Deficiency of Glucose 6 Phosphate Dehydrogenase,Deficiency, G6PD,Deficiency, Glucose-6-Phosphate Dehydrogenase,Dehydrogenase Deficiencies, Glucose-6-Phosphate,Dehydrogenase Deficiencies, Glucosephosphate,Dehydrogenase Deficiency, Glucose-6-Phosphate,Dehydrogenase Deficiency, Glucosephosphate,G6PD Deficiencies,GPD Deficiencies,Glucose-6-Phosphate Dehydrogenase Deficiencies
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D005980	Glutathione Reductase	Catalyzes the oxidation of GLUTATHIONE to GLUTATHIONE DISULFIDE in the presence of NADP+. Deficiency in the enzyme is associated with HEMOLYTIC ANEMIA. Formerly listed as EC 1.6.4.2.	Glutathione-Disulfide Reductase,Reductase, Glutathione,Reductase, Glutathione-Disulfide
D006601	Hexoses	MONOSACCHARIDES whose molecules contain six carbon atoms, such as GLUCOSE and FRUCTOSE. They generally have the chemical formula C6H12O6.	Hexose
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man