Biomaterial Database

Multifactorial drug resistance in an adriamycin-resistant human small cell lung carcinoma cell line. 1987

J G Zijlstra, and E G de Vries, and N H Mulder

In a human small cell lung carcinoma cell line, GLC4, Adriamycin (ADR) resistance was induced. In the resistant cell line, GLC4/ADR, a 45% decreased intracellular ADR level was found compared to GLC4, but this could not fully explain the resistance. Evaluation of DNA damage in both cell lines after incubation with ADR by alkaline and neutral elution revealed single-strand breaks, DNA-protein cross-links, and double-strand breaks (DSB). At all incubation concentrations there was a decreased amount of all types of DNA damage in GLC4/ADR. The number of DSB was decreased also when corrected for the decreased intracellular concentration. This can at least partly be explained by the decreased stability of ADR induced DSB. After removal of ADR, 80% of DSB was repaired in 1 h in GLC4/ADR against no repair in GLC4. X-ray induced DSBs were also repaired faster: in GLC4/ADR t1/2 = 10 min and in GLC4 t1/2 = 23 min. Ratios for single strand breaks/DSBs and single strand breaks/DNA-protein cross-links between GLC4 and GLC4/ADR after exposure to ADR differed; these differences were compatible with differences in the distribution of the various types of DNA damage induced in the cell lines due to an altered ADR-topoisomerase II interaction. In this human small cell lung carcinoma cell line the resistance is multifactorial with decreased intracellular ADR levels, increased DNA repair, and altered ADR-topoisomerase interaction.

UI	MeSH Term	Description	Entries
D008175	Lung Neoplasms	Tumors or cancer of the LUNG.	Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
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
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
D004260	DNA Repair	The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones.	DNA Damage Response
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
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014410	Tumor Stem Cell Assay	A cytologic technique for measuring the functional capacity of tumor stem cells by assaying their activity. It is used primarily for the in vitro testing of antineoplastic agents.	Clonogenic Cell Assay, Tumor,Colony-Forming Units Assay, Tumor,Neoplasm Stem Cell Assay,Stem Cell Assay, Tumor,Colony Forming Units Assay, Tumor
D018288	Carcinoma, Small Cell	An anaplastic, highly malignant, and usually bronchogenic carcinoma composed of small ovoid cells with scanty neoplasm. It is characterized by a dominant, deeply basophilic nucleus, and absent or indistinct nucleoli. (From Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1286-7)	Carcinoma, Oat Cell,Oat Cell Carcinoma,Small Cell Carcinoma,Carcinomas, Oat Cell,Carcinomas, Small Cell,Oat Cell Carcinomas,Small Cell Carcinomas