Development of Resistance and Characteristics of a Human Colon Carcinoma Subline Resistant to Mitoxantrone in vitro
Abstract A subline of human colon carcinoma cells (WiDr/R) resistant to the cytotoxic effects of mitoxantrone in vitro, was developed by continuous exposure to increasing concentrations of drug. After 16 culture passages in the presence of mitoxantrone, a cell population emerged which was 30-40 time...
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| Veröffentlicht in: | Cancer investigation 1987, Vol.5 (5), p.417-428 |
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| container_issue | 5 |
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| container_title | Cancer investigation |
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| creator | Wallace, Roslyn E. Lindh, Dolores Durr, Frederick E. |
| description | Abstract
A subline of human colon carcinoma cells (WiDr/R) resistant to the cytotoxic effects of mitoxantrone in vitro, was developed by continuous exposure to increasing concentrations of drug. After 16 culture passages in the presence of mitoxantrone, a cell population emerged which was 30-40 times more resistant to the cytolytic effect of mitoxantrone than the mitoxantrone-sensitive parent (WiDr/S) line. Resistance to mitoxantrone was retained by WiDr/R cells propagated for more than 40 cell generations in mitoxantrone-free medium. Decreased drug sensitivity was strongly associated with reduced intracellular accumulation of mitoxantrone. Moderate differences in drug retention by sensitive and resistant cells were demonstrated. However, decreased uptake due to alterations at the cell membrane which impair transport of drug into the cell, reducing interaction with DNA, appears to be the principal basis of resistance in these cells. |
| doi_str_mv | 10.3109/07357908709032899 |
| format | Article |
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A subline of human colon carcinoma cells (WiDr/R) resistant to the cytotoxic effects of mitoxantrone in vitro, was developed by continuous exposure to increasing concentrations of drug. After 16 culture passages in the presence of mitoxantrone, a cell population emerged which was 30-40 times more resistant to the cytolytic effect of mitoxantrone than the mitoxantrone-sensitive parent (WiDr/S) line. Resistance to mitoxantrone was retained by WiDr/R cells propagated for more than 40 cell generations in mitoxantrone-free medium. Decreased drug sensitivity was strongly associated with reduced intracellular accumulation of mitoxantrone. Moderate differences in drug retention by sensitive and resistant cells were demonstrated. However, decreased uptake due to alterations at the cell membrane which impair transport of drug into the cell, reducing interaction with DNA, appears to be the principal basis of resistance in these cells.</description><identifier>ISSN: 0735-7907</identifier><identifier>EISSN: 1532-4192</identifier><identifier>DOI: 10.3109/07357908709032899</identifier><identifier>PMID: 3427507</identifier><language>eng</language><publisher>England: Informa UK Ltd</publisher><subject>2,4-Dinitrophenol ; Carcinoma - metabolism ; Carcinoma - pathology ; Cell Nucleus - metabolism ; colon ; Colonic Neoplasms - metabolism ; Colonic Neoplasms - pathology ; Dinitrophenols - pharmacology ; DNA, Neoplasm - metabolism ; Drug Resistance ; Humans ; man ; mitoxantrone ; Mitoxantrone - pharmacokinetics ; Mitoxantrone - pharmacology ; Polysorbates - pharmacology ; tumor cell lines ; Tumor Cells, Cultured - drug effects ; Verapamil - pharmacology</subject><ispartof>Cancer investigation, 1987, Vol.5 (5), p.417-428</ispartof><rights>1987 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 1987</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c347t-38218cab21586da16b4825cdc2d56c11dbab465cc30292dff8d1bf712e1950873</citedby><cites>FETCH-LOGICAL-c347t-38218cab21586da16b4825cdc2d56c11dbab465cc30292dff8d1bf712e1950873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.3109/07357908709032899$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.3109/07357908709032899$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,780,784,4024,27923,27924,27925,59647,59753,60436,60542,61221,61256,61402,61437</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3427507$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wallace, Roslyn E.</creatorcontrib><creatorcontrib>Lindh, Dolores</creatorcontrib><creatorcontrib>Durr, Frederick E.</creatorcontrib><title>Development of Resistance and Characteristics of a Human Colon Carcinoma Subline Resistant to Mitoxantrone in vitro</title><title>Cancer investigation</title><addtitle>Cancer Invest</addtitle><description>Abstract
A subline of human colon carcinoma cells (WiDr/R) resistant to the cytotoxic effects of mitoxantrone in vitro, was developed by continuous exposure to increasing concentrations of drug. After 16 culture passages in the presence of mitoxantrone, a cell population emerged which was 30-40 times more resistant to the cytolytic effect of mitoxantrone than the mitoxantrone-sensitive parent (WiDr/S) line. Resistance to mitoxantrone was retained by WiDr/R cells propagated for more than 40 cell generations in mitoxantrone-free medium. Decreased drug sensitivity was strongly associated with reduced intracellular accumulation of mitoxantrone. Moderate differences in drug retention by sensitive and resistant cells were demonstrated. However, decreased uptake due to alterations at the cell membrane which impair transport of drug into the cell, reducing interaction with DNA, appears to be the principal basis of resistance in these cells.</description><subject>2,4-Dinitrophenol</subject><subject>Carcinoma - metabolism</subject><subject>Carcinoma - pathology</subject><subject>Cell Nucleus - metabolism</subject><subject>colon</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colonic Neoplasms - pathology</subject><subject>Dinitrophenols - pharmacology</subject><subject>DNA, Neoplasm - metabolism</subject><subject>Drug Resistance</subject><subject>Humans</subject><subject>man</subject><subject>mitoxantrone</subject><subject>Mitoxantrone - pharmacokinetics</subject><subject>Mitoxantrone - pharmacology</subject><subject>Polysorbates - pharmacology</subject><subject>tumor cell lines</subject><subject>Tumor Cells, Cultured - drug effects</subject><subject>Verapamil - pharmacology</subject><issn>0735-7907</issn><issn>1532-4192</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1987</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUUuLFDEQDqKs4-oP8CDk5K01j04nQS8yPlZYEXycm-okzWRJJ2OS3nX_vRlmWBBRL1VFfQ-K-hB6SskLTol-SSQXUhMliSacKa3voQ0VnHU91ew-2hzwrhHkQ_SolCtCqGJSnKEz3rdO5AaVt-7ahbRfXKw4zfiLK75UiMZhiBZvd5DBVJfb0ptyYAC-WBeIeJtCahWy8TEtgL-uU_DR3TlUXBP-5Gv62eacGuIjvvZtfIwezBCKe3Lq5-j7-3ffthfd5ecPH7dvLjvDe1k7rhhVBiZGhRos0GHqFRPGGmbFYCi1E0z9IIzhhGlm51lZOs2SMke1aD_h5-j50Xef04_VlTouvhgXAkSX1jJKqTRVA_kvkQoyKDX0jUiPRJNTKdnN4z77BfLtSMl4SGT8I5GmeXYyX6fF2TvFKYKGvz7iPs4pL3CTcrBjhduQ8pxbEr4crP9u_-o3-c5BqDsD2Y1Xac2xPfgfx_0Ck8qstw</recordid><startdate>1987</startdate><enddate>1987</enddate><creator>Wallace, Roslyn E.</creator><creator>Lindh, Dolores</creator><creator>Durr, Frederick E.</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>1987</creationdate><title>Development of Resistance and Characteristics of a Human Colon Carcinoma Subline Resistant to Mitoxantrone in vitro</title><author>Wallace, Roslyn E. ; Lindh, Dolores ; Durr, Frederick E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c347t-38218cab21586da16b4825cdc2d56c11dbab465cc30292dff8d1bf712e1950873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1987</creationdate><topic>2,4-Dinitrophenol</topic><topic>Carcinoma - metabolism</topic><topic>Carcinoma - pathology</topic><topic>Cell Nucleus - metabolism</topic><topic>colon</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Colonic Neoplasms - pathology</topic><topic>Dinitrophenols - pharmacology</topic><topic>DNA, Neoplasm - metabolism</topic><topic>Drug Resistance</topic><topic>Humans</topic><topic>man</topic><topic>mitoxantrone</topic><topic>Mitoxantrone - pharmacokinetics</topic><topic>Mitoxantrone - pharmacology</topic><topic>Polysorbates - pharmacology</topic><topic>tumor cell lines</topic><topic>Tumor Cells, Cultured - drug effects</topic><topic>Verapamil - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wallace, Roslyn E.</creatorcontrib><creatorcontrib>Lindh, Dolores</creatorcontrib><creatorcontrib>Durr, Frederick E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wallace, Roslyn E.</au><au>Lindh, Dolores</au><au>Durr, Frederick E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of Resistance and Characteristics of a Human Colon Carcinoma Subline Resistant to Mitoxantrone in vitro</atitle><jtitle>Cancer investigation</jtitle><addtitle>Cancer Invest</addtitle><date>1987</date><risdate>1987</risdate><volume>5</volume><issue>5</issue><spage>417</spage><epage>428</epage><pages>417-428</pages><issn>0735-7907</issn><eissn>1532-4192</eissn><abstract>Abstract
A subline of human colon carcinoma cells (WiDr/R) resistant to the cytotoxic effects of mitoxantrone in vitro, was developed by continuous exposure to increasing concentrations of drug. After 16 culture passages in the presence of mitoxantrone, a cell population emerged which was 30-40 times more resistant to the cytolytic effect of mitoxantrone than the mitoxantrone-sensitive parent (WiDr/S) line. Resistance to mitoxantrone was retained by WiDr/R cells propagated for more than 40 cell generations in mitoxantrone-free medium. Decreased drug sensitivity was strongly associated with reduced intracellular accumulation of mitoxantrone. Moderate differences in drug retention by sensitive and resistant cells were demonstrated. However, decreased uptake due to alterations at the cell membrane which impair transport of drug into the cell, reducing interaction with DNA, appears to be the principal basis of resistance in these cells.</abstract><cop>England</cop><pub>Informa UK Ltd</pub><pmid>3427507</pmid><doi>10.3109/07357908709032899</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0735-7907 |
| ispartof | Cancer investigation, 1987, Vol.5 (5), p.417-428 |
| issn | 0735-7907 1532-4192 |
| language | eng |
| recordid | cdi_informahealthcare_journals_10_3109_07357908709032899 |
| source | MEDLINE; Taylor & Francis Medical Library - CRKN; Taylor & Francis Journals Complete |
| subjects | 2,4-Dinitrophenol Carcinoma - metabolism Carcinoma - pathology Cell Nucleus - metabolism colon Colonic Neoplasms - metabolism Colonic Neoplasms - pathology Dinitrophenols - pharmacology DNA, Neoplasm - metabolism Drug Resistance Humans man mitoxantrone Mitoxantrone - pharmacokinetics Mitoxantrone - pharmacology Polysorbates - pharmacology tumor cell lines Tumor Cells, Cultured - drug effects Verapamil - pharmacology |
| title | Development of Resistance and Characteristics of a Human Colon Carcinoma Subline Resistant to Mitoxantrone in vitro |
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