DNA repair rate and etoposide (VP16) resistance of tumor cell subpopulations derived from a single human small cell lung cancer.

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

DNA repair rate and etoposide (VP16) resistance of tumor cell subpopulations derived from a single human small cell lung cancer. / Hansen, Lasse Tengbjerg; Lundin, Cecilia; Helleday, Thomas; Poulsen, Hans Skovgaard; Sørensen, Claus Storgaard; Petersen, Lone Nørgård; Spang-Thomsen, Mogens.

In: Lung Cancer, Vol. 40, No. 2, 2003, p. 157-64.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Hansen, LT, Lundin, C, Helleday, T, Poulsen, HS, Sørensen, CS, Petersen, LN & Spang-Thomsen, M 2003, 'DNA repair rate and etoposide (VP16) resistance of tumor cell subpopulations derived from a single human small cell lung cancer.', Lung Cancer, vol. 40, no. 2, pp. 157-64.

APA

Hansen, L. T., Lundin, C., Helleday, T., Poulsen, H. S., Sørensen, C. S., Petersen, L. N., & Spang-Thomsen, M. (2003). DNA repair rate and etoposide (VP16) resistance of tumor cell subpopulations derived from a single human small cell lung cancer. Lung Cancer, 40(2), 157-64.

Vancouver

Hansen LT, Lundin C, Helleday T, Poulsen HS, Sørensen CS, Petersen LN et al. DNA repair rate and etoposide (VP16) resistance of tumor cell subpopulations derived from a single human small cell lung cancer. Lung Cancer. 2003;40(2):157-64.

Author

Hansen, Lasse Tengbjerg ; Lundin, Cecilia ; Helleday, Thomas ; Poulsen, Hans Skovgaard ; Sørensen, Claus Storgaard ; Petersen, Lone Nørgård ; Spang-Thomsen, Mogens. / DNA repair rate and etoposide (VP16) resistance of tumor cell subpopulations derived from a single human small cell lung cancer. In: Lung Cancer. 2003 ; Vol. 40, No. 2. pp. 157-64.

Bibtex

@article{8f9e4f70abff11ddb5e9000ea68e967b,
title = "DNA repair rate and etoposide (VP16) resistance of tumor cell subpopulations derived from a single human small cell lung cancer.",
abstract = "Two human small cell lung cancer (SCLC) subpopulations, CPH 54A, and CPH 54B, established from the same patient tumor by in vitro cloning, were investigated. The tumor was classified as intermediate-type SCLC. The cellular sensitivity to ionizing radiation (IR) was previously determined in the two sublines both in vivo and in vitro. Here we measured the etoposide (VP16) sensitivity together with the induction and repair of VP16- and IR-induced DNA double-strand breaks (DSBs). The two subpopulations were found to differ significantly in sensitivity to VP16, with the radioresistant 54B subline also being VP16 resistant. In order to explain the VP16 resistant phenotype several mechanisms where considered. The p53 status, P-glycoprotein, MRP, topoisomerase IIalpha, and Mre11 protein levels, as well as growth kinetics, provided no explanations of the observed VP16 resistance. In contrast, a significant difference in repair of both VP16- and IR-induced DSBs, together with a difference in the levels of the DSB repair proteins DNA-dependent protein kinase (DNA-PK(cs)) and RAD51 was observed. The VP16- and radioresistant 54B subline exhibited a pronounced higher repair rate of DSBs and higher protein levels of both DNA-PK(cs) and RAD51 compared with the sensitive 54A subline. We suggest, that different DSB repair rates among tumor cell subpopulations of individual SCLC tumors may be a major determinant for the variation in clinical treatment effect observed in human SCLC tumors of identical histological subtype.",
author = "Hansen, {Lasse Tengbjerg} and Cecilia Lundin and Thomas Helleday and Poulsen, {Hans Skovgaard} and S{\o}rensen, {Claus Storgaard} and Petersen, {Lone N{\o}rg{\aa}rd} and Mogens Spang-Thomsen",
note = "Keywords: Antineoplastic Agents, Phytogenic; Carcinoma, Small Cell; DNA Damage; DNA Repair; DNA Topoisomerases, Type II; DNA, Neoplasm; DNA-Activated Protein Kinase; DNA-Binding Proteins; Drug Resistance, Neoplasm; Endodeoxyribonucleases; Etoposide; Exodeoxyribonucleases; Humans; Lung Neoplasms; Nuclear Proteins; P-Glycoprotein; P-Glycoproteins; Protein-Serine-Threonine Kinases; Rad51 Recombinase; Saccharomyces cerevisiae Proteins; Tumor Cells, Cultured; Tumor Suppressor Protein p53",
year = "2003",
language = "English",
volume = "40",
pages = "157--64",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

RIS

TY - JOUR

T1 - DNA repair rate and etoposide (VP16) resistance of tumor cell subpopulations derived from a single human small cell lung cancer.

AU - Hansen, Lasse Tengbjerg

AU - Lundin, Cecilia

AU - Helleday, Thomas

AU - Poulsen, Hans Skovgaard

AU - Sørensen, Claus Storgaard

AU - Petersen, Lone Nørgård

AU - Spang-Thomsen, Mogens

N1 - Keywords: Antineoplastic Agents, Phytogenic; Carcinoma, Small Cell; DNA Damage; DNA Repair; DNA Topoisomerases, Type II; DNA, Neoplasm; DNA-Activated Protein Kinase; DNA-Binding Proteins; Drug Resistance, Neoplasm; Endodeoxyribonucleases; Etoposide; Exodeoxyribonucleases; Humans; Lung Neoplasms; Nuclear Proteins; P-Glycoprotein; P-Glycoproteins; Protein-Serine-Threonine Kinases; Rad51 Recombinase; Saccharomyces cerevisiae Proteins; Tumor Cells, Cultured; Tumor Suppressor Protein p53

PY - 2003

Y1 - 2003

N2 - Two human small cell lung cancer (SCLC) subpopulations, CPH 54A, and CPH 54B, established from the same patient tumor by in vitro cloning, were investigated. The tumor was classified as intermediate-type SCLC. The cellular sensitivity to ionizing radiation (IR) was previously determined in the two sublines both in vivo and in vitro. Here we measured the etoposide (VP16) sensitivity together with the induction and repair of VP16- and IR-induced DNA double-strand breaks (DSBs). The two subpopulations were found to differ significantly in sensitivity to VP16, with the radioresistant 54B subline also being VP16 resistant. In order to explain the VP16 resistant phenotype several mechanisms where considered. The p53 status, P-glycoprotein, MRP, topoisomerase IIalpha, and Mre11 protein levels, as well as growth kinetics, provided no explanations of the observed VP16 resistance. In contrast, a significant difference in repair of both VP16- and IR-induced DSBs, together with a difference in the levels of the DSB repair proteins DNA-dependent protein kinase (DNA-PK(cs)) and RAD51 was observed. The VP16- and radioresistant 54B subline exhibited a pronounced higher repair rate of DSBs and higher protein levels of both DNA-PK(cs) and RAD51 compared with the sensitive 54A subline. We suggest, that different DSB repair rates among tumor cell subpopulations of individual SCLC tumors may be a major determinant for the variation in clinical treatment effect observed in human SCLC tumors of identical histological subtype.

AB - Two human small cell lung cancer (SCLC) subpopulations, CPH 54A, and CPH 54B, established from the same patient tumor by in vitro cloning, were investigated. The tumor was classified as intermediate-type SCLC. The cellular sensitivity to ionizing radiation (IR) was previously determined in the two sublines both in vivo and in vitro. Here we measured the etoposide (VP16) sensitivity together with the induction and repair of VP16- and IR-induced DNA double-strand breaks (DSBs). The two subpopulations were found to differ significantly in sensitivity to VP16, with the radioresistant 54B subline also being VP16 resistant. In order to explain the VP16 resistant phenotype several mechanisms where considered. The p53 status, P-glycoprotein, MRP, topoisomerase IIalpha, and Mre11 protein levels, as well as growth kinetics, provided no explanations of the observed VP16 resistance. In contrast, a significant difference in repair of both VP16- and IR-induced DSBs, together with a difference in the levels of the DSB repair proteins DNA-dependent protein kinase (DNA-PK(cs)) and RAD51 was observed. The VP16- and radioresistant 54B subline exhibited a pronounced higher repair rate of DSBs and higher protein levels of both DNA-PK(cs) and RAD51 compared with the sensitive 54A subline. We suggest, that different DSB repair rates among tumor cell subpopulations of individual SCLC tumors may be a major determinant for the variation in clinical treatment effect observed in human SCLC tumors of identical histological subtype.

M3 - Journal article

C2 - 12711116

VL - 40

SP - 157

EP - 164

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

IS - 2

ER -

ID: 8442224