Comparative effects of doxorubicin and 4'-epi-doxorubicin on nucleic acid metabolism and cytotoxicity in a human tumor cell line. 1990

O Cantoni, and P Sestili, and F Cattabeni, and C Geroni, and F Giuliani
Istituto di Farmacologia e Farmacognosia, Universita' degli Studi di Urbino, Italy.

The effects of 4'-epi-doxorubicin (4'E-Dx) and doxorubicin (Dx) on cell survival were investigated after treatments for 1 or 24 h. It was found that after short-term exposure, 4'E-Dx causes a higher level of killing than Dx, whereas a similar cytotoxic response is detectable after 24 h. Under the same experimental conditions (treatment for 1 or 24 h) at equimolar concentrations, the two anthracyclines were equally inhibitory to DNA or RNA synthesis. Both the degree and the rate of induction of DNA strand breakage over a 1-h drug exposure were higher for 4'E-Dx than for Dx. These data were related to results of experiments carried out to investigate the rates of uptake and egress of the anthracyclines. From this study we concluded that no relationship can be established between the cytotoxicity of 4'E-Dx and Dx and their ability to inhibit DNA and RNA synthesis. In addition, the different DNA-damaging action of the two drugs does not appear to be solely dependent on the different rates of cellular uptake.

UI MeSH Term Description Entries
D009696 Nucleic Acids High molecular weight polymers containing a mixture of purine and pyrimidine nucleotides chained together by ribose or deoxyribose linkages. Nucleic Acid,Acid, Nucleic,Acids, Nucleic
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012313 RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015251 Epirubicin An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA. 4'-Epiadriamycin,4'-Epidoxorubicin,4'-Epi-Adriamycin,4'-Epi-DXR,4'-Epi-Doxorubicin,EPI-cell,Ellence,Epilem,Epirubicin Hydrochloride,Farmorubicin,Farmorubicina,Farmorubicine,IMI-28,NSC-256942,Pharmorubicin,4' Epi Adriamycin,4' Epi DXR,4' Epi Doxorubicin,4' Epiadriamycin,4' Epidoxorubicin,EPI cell,EPIcell,Hydrochloride, Epirubicin,IMI 28,IMI28,NSC 256942,NSC256942

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