PMID: 8588998Nov 1, 1995Paper

Qualitatively different mechanisms of resistance to doxorubicin, both involving altered glutathione pools, in two myeloid cell lines in vitro

Pediatric Hematology and Oncology
L K DajaniL Slørdal

Abstract

Subclones of the two well-characterized myeloid cell lines HL-60 and KG1a were selected for doxorubicin resistance by systematic exposure to increased concentrations of the drug in vitro. Both subclones demonstrated a threefold increased resistance to the drug as evident from cell growth in liquid culture and clonogenicity in a semisolid matrix. Both resistant subclones displayed a similar degree of reduced total and nuclear doxorubicin levels. The HL-60 and the KG1a cells differed qualitatively and quantitatively with respect to glutathione (GSH) levels during culture, with markedly elevated concentrations in the resistant HL-60 subclone during 1 week of culture. Total GSH pools in resistant and sensitive KG1a cells were similar, but maximum GSH levels were reached earlier in the resistant KG1a clones than in the parental cells. Northern blot analysis suggests that resistance was accompanied by increased mdr1 expression in the KG1a but not in the HL-60 cells, whereas alterations in the glutathione S-transferase P1-1 and topoisomerase II message was evident in the latter. The results demonstrate the complex, multifactorial mechanisms behind the in vitro induction of even moderate resistance in anthracyclines.

References

Jan 1, 1992·Acta Oncologica·A L Harris, D Hochhauser
Jan 1, 1992·Cancer Chemotherapy and Pharmacology·C P VendrikP A Steerenberg
Jan 1, 1991·Pharmacology & Therapeutics·S M Black, C R Wolf
Sep 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J A MoscowK H Cowan
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·M Tsai-PflugfelderJ C Wang
Aug 1, 1993·Pharmacology & Toxicology·L SlørdalD J Warren

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.