The effect of different chemotherapeutic agents on the enrichment of DNA mismatch repair-deficient tumour cells
Loss of DNA mismatch repair is a common finding in hereditary non-polyposis colon cancer as well as in many types of sporadic human tumours. We compared the effect of loss of DNA mismatch repair on drug sensitivity as measured by a clonogenic assay with its effect on the ability of the same drug to enrich for mismatch repair-deficient cells in a proliferating tumour cell population. Mixed populations containing 50% DNA mismatch repair-deficient cells constitutively expressing green fluorescent protein and 50% mismatch repair-proficient cells were exposed to different chemotherapeutic agents. 6-Thioguanine, to which DNA mismatch repair-deficient cells are known to be resistant, was included as a control. The results in the cytotoxicity assays and in the enrichment experiments were concordant. Treatment with either carboplatin, cisplatin, doxorubicin, etoposide or 6-thioguanine resulted in enrichment for mismatch repair-deficient cells, and clonogenic assays demonstrated resistance to these agents, which varied from 1.3- to 4.8-fold. Treatment with melphalan, paclitaxel, perfosfamide or tamoxifen failed to enrich for mismatch repair-deficient cells, and no change in sensitivity to these agents was detected in the clonogenic assays. These results identify the topoisomerase II inhibitors etoposide and doxorubicin as additional agents for which loss of DNA mismatch repair causes drug resistance. The concordance of the results from the two assay systems validates the enrichment assay as a rapid and reliable method for screening for the effect of loss of DNA mismatch repair on sensitivity to additional drugs.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
1998 |
|---|---|
| Erschienen: |
1998 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:77 |
|---|---|
| Enthalten in: |
British journal of cancer - 77(1998), 5 vom: 19. März, Seite 703-8 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Fink, D [VerfasserIn] |
|---|
| Anmerkungen: |
Date Completed 02.04.1998 Date Revised 15.05.2019 published: Print Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM09455661X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM09455661X | ||
| 003 | DE-627 | ||
| 005 | 20231222095926.0 | ||
| 007 | tu | ||
| 008 | 231222s1998 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0316.xml |
| 035 | |a (DE-627)NLM09455661X | ||
| 035 | |a (NLM)9514047 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Fink, D |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The effect of different chemotherapeutic agents on the enrichment of DNA mismatch repair-deficient tumour cells |
| 264 | 1 | |c 1998 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 02.04.1998 | ||
| 500 | |a Date Revised 15.05.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Loss of DNA mismatch repair is a common finding in hereditary non-polyposis colon cancer as well as in many types of sporadic human tumours. We compared the effect of loss of DNA mismatch repair on drug sensitivity as measured by a clonogenic assay with its effect on the ability of the same drug to enrich for mismatch repair-deficient cells in a proliferating tumour cell population. Mixed populations containing 50% DNA mismatch repair-deficient cells constitutively expressing green fluorescent protein and 50% mismatch repair-proficient cells were exposed to different chemotherapeutic agents. 6-Thioguanine, to which DNA mismatch repair-deficient cells are known to be resistant, was included as a control. The results in the cytotoxicity assays and in the enrichment experiments were concordant. Treatment with either carboplatin, cisplatin, doxorubicin, etoposide or 6-thioguanine resulted in enrichment for mismatch repair-deficient cells, and clonogenic assays demonstrated resistance to these agents, which varied from 1.3- to 4.8-fold. Treatment with melphalan, paclitaxel, perfosfamide or tamoxifen failed to enrich for mismatch repair-deficient cells, and no change in sensitivity to these agents was detected in the clonogenic assays. These results identify the topoisomerase II inhibitors etoposide and doxorubicin as additional agents for which loss of DNA mismatch repair causes drug resistance. The concordance of the results from the two assay systems validates the enrichment assay as a rapid and reliable method for screening for the effect of loss of DNA mismatch repair on sensitivity to additional drugs | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a DNA, Neoplasm |2 NLM | |
| 650 | 7 | |a Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Tamoxifen |2 NLM | |
| 650 | 7 | |a 094ZI81Y45 |2 NLM | |
| 650 | 7 | |a Etoposide |2 NLM | |
| 650 | 7 | |a 6PLQ3CP4P3 |2 NLM | |
| 650 | 7 | |a Doxorubicin |2 NLM | |
| 650 | 7 | |a 80168379AG |2 NLM | |
| 650 | 7 | |a Cyclophosphamide |2 NLM | |
| 650 | 7 | |a 8N3DW7272P |2 NLM | |
| 650 | 7 | |a Carboplatin |2 NLM | |
| 650 | 7 | |a BG3F62OND5 |2 NLM | |
| 650 | 7 | |a Thioguanine |2 NLM | |
| 650 | 7 | |a FTK8U1GZNX |2 NLM | |
| 650 | 7 | |a Paclitaxel |2 NLM | |
| 650 | 7 | |a P88XT4IS4D |2 NLM | |
| 650 | 7 | |a Cisplatin |2 NLM | |
| 650 | 7 | |a Q20Q21Q62J |2 NLM | |
| 650 | 7 | |a Melphalan |2 NLM | |
| 650 | 7 | |a Q41OR9510P |2 NLM | |
| 650 | 7 | |a perfosfamide |2 NLM | |
| 650 | 7 | |a U880A4FUDA |2 NLM | |
| 700 | 1 | |a Nebel, S |e verfasserin |4 aut | |
| 700 | 1 | |a Norris, P S |e verfasserin |4 aut | |
| 700 | 1 | |a Aebi, S |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, H K |e verfasserin |4 aut | |
| 700 | 1 | |a Haas, M |e verfasserin |4 aut | |
| 700 | 1 | |a Howell, S B |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t British journal of cancer |d 1947 |g 77(1998), 5 vom: 19. März, Seite 703-8 |w (DE-627)NLM000027537 |x 1532-1827 |7 nnns |
| 773 | 1 | 8 | |g volume:77 |g year:1998 |g number:5 |g day:19 |g month:03 |g pages:703-8 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 77 |j 1998 |e 5 |b 19 |c 03 |h 703-8 | ||