Enhanced dna repair and tolerance of DNA damage associated with resistance to cis-diammine-dichloroplatinum (II) after in vitro exposure of a human teratoma cell line to fractionated X-irradiation

In vitro exposure of a human testicular teratoma continuous cell line to fractionated X-irradiation resulted in the expression of resistance to cisplatin. In two independently-derived sublines, designated SUSA-DXR 3 and SUSADXR 10 resulting from treatment with either 13 fractions of 1.5 Gy (dose req...

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Veröffentlicht in:International journal of radiation oncology, biology, physics biology, physics, 1990-07, Vol.19 (1), p.75-83
Hauptverfasser: Hill, Bridget T., Shellard, Sharon A., Hosking, Louise K., Fichtinger-Schepman, Anne Marie J., Bedford, Philip
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container_issue 1
container_start_page 75
container_title International journal of radiation oncology, biology, physics
container_volume 19
creator Hill, Bridget T.
Shellard, Sharon A.
Hosking, Louise K.
Fichtinger-Schepman, Anne Marie J.
Bedford, Philip
description In vitro exposure of a human testicular teratoma continuous cell line to fractionated X-irradiation resulted in the expression of resistance to cisplatin. In two independently-derived sublines, designated SUSA-DXR 3 and SUSADXR 10 resulting from treatment with either 13 fractions of 1.5 Gy (dose required to reduce survival by 1 log) or 10 fractions of 3 Gy (dose required to reduce survival by 2 logs) respectivves, the IC 50 values for cisplatin were 2− and 3.1-fold higher than that of the parental cell line. These sublines were cross-resistant to carboplatin (approximately 2-fold) but not to adriamycin and they showed unaltered radiosensitivities. The SUSA-DXR 10 subline expressed some cross-resistance to mitomycin C and melphalan but none to Carmustine (BCNU). Total glutathione content was significantly reduced in both SUSA-DXR 10 and SUSA-DXR 13 cells, but the activities of associated enzymes, including the glutathione S-transferases, peroxidase and reductase were not modified significantly in the resistant sublines. Resistance in the SUSA-DXR 10 subline was associated with significantly decreased 195mcisplatin uptake (p < 0.01), but this was not reflected in a reduced level of drug bound to the DNA. The formation and removal of four platinum DNA adducts were immunochemically quantitated. Immediately following drug treatment there was a higher level of total platination of the DNA in the resistant subline indicative of increased tolerance to DNA damage. After an 18 hr post treatment incubation, there was an indication of some repair capacity in this SUSA-DXR 10 cell line, which was not apparent in the parental cells. Neither the parental nor the SUSA-DXR 10 cell line was proficient in the repair of the major adduct Pt-GG, whereas both lines repaired the monofunctional adduct and the adduct Pt(GMP) 2. SUSA-DXR 10 cells were also able to repair the intrastrand adduct Pt-AG and interstrand crosslinks, unlike the repair deficient parental cells. Higher levels of interstrand crosslinks were characteristic of the SUSA-DXR 10 subline. These observations therefore implicate both enhanced repair and increased tolerance of DNA damage as mechanisms of resistance to cisplatin resulting from in vitro exposure of a human teratoma cell line to fractionated X-irradiation.
doi_str_mv 10.1016/0360-3016(90)90137-9
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In two independently-derived sublines, designated SUSA-DXR 3 and SUSADXR 10 resulting from treatment with either 13 fractions of 1.5 Gy (dose required to reduce survival by 1 log) or 10 fractions of 3 Gy (dose required to reduce survival by 2 logs) respectivves, the IC 50 values for cisplatin were 2− and 3.1-fold higher than that of the parental cell line. These sublines were cross-resistant to carboplatin (approximately 2-fold) but not to adriamycin and they showed unaltered radiosensitivities. The SUSA-DXR 10 subline expressed some cross-resistance to mitomycin C and melphalan but none to Carmustine (BCNU). Total glutathione content was significantly reduced in both SUSA-DXR 10 and SUSA-DXR 13 cells, but the activities of associated enzymes, including the glutathione S-transferases, peroxidase and reductase were not modified significantly in the resistant sublines. Resistance in the SUSA-DXR 10 subline was associated with significantly decreased 195mcisplatin uptake (p &lt; 0.01), but this was not reflected in a reduced level of drug bound to the DNA. The formation and removal of four platinum DNA adducts were immunochemically quantitated. Immediately following drug treatment there was a higher level of total platination of the DNA in the resistant subline indicative of increased tolerance to DNA damage. After an 18 hr post treatment incubation, there was an indication of some repair capacity in this SUSA-DXR 10 cell line, which was not apparent in the parental cells. Neither the parental nor the SUSA-DXR 10 cell line was proficient in the repair of the major adduct Pt-GG, whereas both lines repaired the monofunctional adduct and the adduct Pt(GMP) 2. SUSA-DXR 10 cells were also able to repair the intrastrand adduct Pt-AG and interstrand crosslinks, unlike the repair deficient parental cells. Higher levels of interstrand crosslinks were characteristic of the SUSA-DXR 10 subline. These observations therefore implicate both enhanced repair and increased tolerance of DNA damage as mechanisms of resistance to cisplatin resulting from in vitro exposure of a human teratoma cell line to fractionated X-irradiation.</description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/0360-3016(90)90137-9</identifier><identifier>PMID: 2380098</identifier><identifier>CODEN: IOBPD3</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>ANIMAL CELLS ; ANIMALS ; ANTINEOPLASTIC DRUGS ; Biological and medical sciences ; BIOLOGICAL RECOVERY ; BIOLOGICAL REPAIR ; BODY ; Cisplatin ; Cisplatin - metabolism ; Cisplatin - pharmacokinetics ; Cisplatin - pharmacology ; DISEASES ; DNA - drug effects ; DNA - metabolism ; DNA Adducts ; DNA Damage ; DNA damage and repair ; DNA REPAIR ; DNA Repair - radiation effects ; Dose-Response Relationship, Drug ; DOSE-RESPONSE RELATIONSHIPS ; DOSES ; Drug resistance ; Drug Resistance - radiation effects ; DRUGS ; ENZYMES ; FRACTIONATED IRRADIATION ; Genital system. Mammary gland ; GLUTATHIONE ; Glutathione - metabolism ; Glutathione Peroxidase - metabolism ; Glutathione Reductase - metabolism ; Glutathione Transferase - metabolism ; GONADS ; Humans ; IN VITRO ; IRRADIATION ; Male ; MALE GENITALS ; MAMMALS ; MAN ; Medical sciences ; NEOPLASMS ; ORGANIC COMPOUNDS ; ORGANS ; OXIDOREDUCTASES ; PEPTIDES ; PEROXIDASES ; POLYPEPTIDES ; PRIMATES ; PROTEINS ; Radiation ; RADIATION DOSES ; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT ; RADIOPROTECTIVE SUBSTANCES ; RADIOSENSITIVITY ; Radiotherapy Dosage ; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) ; RECOVERY ; REPAIR ; Teratoma - enzymology ; Teratoma - metabolism ; Teratoma - pathology ; TESTES ; Testicular Neoplasms - enzymology ; Testicular Neoplasms - metabolism ; Testicular Neoplasms - pathology ; Time Factors ; TRANSFERASES ; TUMOR CELLS ; Tumor Cells, Cultured - enzymology ; Tumor Cells, Cultured - radiation effects ; VERTEBRATES 560120 -- Radiation Effects on Biochemicals, Cells, &amp; Tissue Culture</subject><ispartof>International journal of radiation oncology, biology, physics, 1990-07, Vol.19 (1), p.75-83</ispartof><rights>1990</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c328t-18bce0fd3f8427534acf617f94d412841e6d75ed5934eb371f80d3215707ff73</citedby><cites>FETCH-LOGICAL-c328t-18bce0fd3f8427534acf617f94d412841e6d75ed5934eb371f80d3215707ff73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0360-3016(90)90137-9$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=4649867$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2380098$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/6616416$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Hill, Bridget T.</creatorcontrib><creatorcontrib>Shellard, Sharon A.</creatorcontrib><creatorcontrib>Hosking, Louise K.</creatorcontrib><creatorcontrib>Fichtinger-Schepman, Anne Marie J.</creatorcontrib><creatorcontrib>Bedford, Philip</creatorcontrib><title>Enhanced dna repair and tolerance of DNA damage associated with resistance to cis-diammine-dichloroplatinum (II) after in vitro exposure of a human teratoma cell line to fractionated X-irradiation</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description>In vitro exposure of a human testicular teratoma continuous cell line to fractionated X-irradiation resulted in the expression of resistance to cisplatin. In two independently-derived sublines, designated SUSA-DXR 3 and SUSADXR 10 resulting from treatment with either 13 fractions of 1.5 Gy (dose required to reduce survival by 1 log) or 10 fractions of 3 Gy (dose required to reduce survival by 2 logs) respectivves, the IC 50 values for cisplatin were 2− and 3.1-fold higher than that of the parental cell line. These sublines were cross-resistant to carboplatin (approximately 2-fold) but not to adriamycin and they showed unaltered radiosensitivities. The SUSA-DXR 10 subline expressed some cross-resistance to mitomycin C and melphalan but none to Carmustine (BCNU). Total glutathione content was significantly reduced in both SUSA-DXR 10 and SUSA-DXR 13 cells, but the activities of associated enzymes, including the glutathione S-transferases, peroxidase and reductase were not modified significantly in the resistant sublines. Resistance in the SUSA-DXR 10 subline was associated with significantly decreased 195mcisplatin uptake (p &lt; 0.01), but this was not reflected in a reduced level of drug bound to the DNA. The formation and removal of four platinum DNA adducts were immunochemically quantitated. Immediately following drug treatment there was a higher level of total platination of the DNA in the resistant subline indicative of increased tolerance to DNA damage. After an 18 hr post treatment incubation, there was an indication of some repair capacity in this SUSA-DXR 10 cell line, which was not apparent in the parental cells. Neither the parental nor the SUSA-DXR 10 cell line was proficient in the repair of the major adduct Pt-GG, whereas both lines repaired the monofunctional adduct and the adduct Pt(GMP) 2. SUSA-DXR 10 cells were also able to repair the intrastrand adduct Pt-AG and interstrand crosslinks, unlike the repair deficient parental cells. Higher levels of interstrand crosslinks were characteristic of the SUSA-DXR 10 subline. These observations therefore implicate both enhanced repair and increased tolerance of DNA damage as mechanisms of resistance to cisplatin resulting from in vitro exposure of a human teratoma cell line to fractionated X-irradiation.</description><subject>ANIMAL CELLS</subject><subject>ANIMALS</subject><subject>ANTINEOPLASTIC DRUGS</subject><subject>Biological and medical sciences</subject><subject>BIOLOGICAL RECOVERY</subject><subject>BIOLOGICAL REPAIR</subject><subject>BODY</subject><subject>Cisplatin</subject><subject>Cisplatin - metabolism</subject><subject>Cisplatin - pharmacokinetics</subject><subject>Cisplatin - pharmacology</subject><subject>DISEASES</subject><subject>DNA - drug effects</subject><subject>DNA - metabolism</subject><subject>DNA Adducts</subject><subject>DNA Damage</subject><subject>DNA damage and repair</subject><subject>DNA REPAIR</subject><subject>DNA Repair - radiation effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>DOSE-RESPONSE RELATIONSHIPS</subject><subject>DOSES</subject><subject>Drug resistance</subject><subject>Drug Resistance - radiation effects</subject><subject>DRUGS</subject><subject>ENZYMES</subject><subject>FRACTIONATED IRRADIATION</subject><subject>Genital system. Mammary gland</subject><subject>GLUTATHIONE</subject><subject>Glutathione - metabolism</subject><subject>Glutathione Peroxidase - metabolism</subject><subject>Glutathione Reductase - metabolism</subject><subject>Glutathione Transferase - metabolism</subject><subject>GONADS</subject><subject>Humans</subject><subject>IN VITRO</subject><subject>IRRADIATION</subject><subject>Male</subject><subject>MALE GENITALS</subject><subject>MAMMALS</subject><subject>MAN</subject><subject>Medical sciences</subject><subject>NEOPLASMS</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANS</subject><subject>OXIDOREDUCTASES</subject><subject>PEPTIDES</subject><subject>PEROXIDASES</subject><subject>POLYPEPTIDES</subject><subject>PRIMATES</subject><subject>PROTEINS</subject><subject>Radiation</subject><subject>RADIATION DOSES</subject><subject>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</subject><subject>RADIOPROTECTIVE SUBSTANCES</subject><subject>RADIOSENSITIVITY</subject><subject>Radiotherapy Dosage</subject><subject>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</subject><subject>RECOVERY</subject><subject>REPAIR</subject><subject>Teratoma - enzymology</subject><subject>Teratoma - metabolism</subject><subject>Teratoma - pathology</subject><subject>TESTES</subject><subject>Testicular Neoplasms - enzymology</subject><subject>Testicular Neoplasms - metabolism</subject><subject>Testicular Neoplasms - pathology</subject><subject>Time Factors</subject><subject>TRANSFERASES</subject><subject>TUMOR CELLS</subject><subject>Tumor Cells, Cultured - enzymology</subject><subject>Tumor Cells, Cultured - radiation effects</subject><subject>VERTEBRATES 560120 -- Radiation Effects on Biochemicals, Cells, &amp; Tissue Culture</subject><issn>0360-3016</issn><issn>1879-355X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9u1DAQxiMEKtvCG4BkIQ7tIWDHjh1fkKq2wEoVXHroLZr1H2KU2CvbW-D9eDDs3dUeOXnk-X0zn-ZrmjcEfyCY8I-YctzSUl1KfCUxoaKVz5oVGYRsad8_Pm9WJ-Rlc57ST4wxIYKdNWcdHTCWw6r5e-cn8MpopD2gaLbgIgKvUQ6zibWDgkW3366RhgV-GAQpBeUgF8Uvl6ciSS7lPZgDUi612sGyOG9KoaY5xLCdITu_W9Dlen2FwGYTkfPoyeUYkPm9DWkX92sATbsFPCoA5LAAUmae0Vxm1dk2gsou-P3ux9bFCGVV_XnVvLAwJ_P6-F40D5_vHm6-tvffv6xvru9bRbsht2TYKIOtpnZgnegpA2U5EVYyzUg3MGK4Fr3RvaTMbKggdsCadqQXWFgr6EXz7jA2pOzGpFw2alLBe6PyyDnhjPACsQOkYkgpGjtuo1sg_hkJHmtuYw1lrKGMEo_73EZZZG8Psu1usxh9Eh2DKv33xz4kBbOt0bh0whhncuDV4qcDZsoZnpyJ1aap-bpYXerg_u_jH_eutrg</recordid><startdate>199007</startdate><enddate>199007</enddate><creator>Hill, Bridget T.</creator><creator>Shellard, Sharon A.</creator><creator>Hosking, Louise K.</creator><creator>Fichtinger-Schepman, Anne Marie J.</creator><creator>Bedford, Philip</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>OTOTI</scope></search><sort><creationdate>199007</creationdate><title>Enhanced dna repair and tolerance of DNA damage associated with resistance to cis-diammine-dichloroplatinum (II) after in vitro exposure of a human teratoma cell line to fractionated X-irradiation</title><author>Hill, Bridget T. ; Shellard, Sharon A. ; Hosking, Louise K. ; Fichtinger-Schepman, Anne Marie J. ; Bedford, Philip</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c328t-18bce0fd3f8427534acf617f94d412841e6d75ed5934eb371f80d3215707ff73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>ANIMAL CELLS</topic><topic>ANIMALS</topic><topic>ANTINEOPLASTIC DRUGS</topic><topic>Biological and medical sciences</topic><topic>BIOLOGICAL RECOVERY</topic><topic>BIOLOGICAL REPAIR</topic><topic>BODY</topic><topic>Cisplatin</topic><topic>Cisplatin - metabolism</topic><topic>Cisplatin - pharmacokinetics</topic><topic>Cisplatin - pharmacology</topic><topic>DISEASES</topic><topic>DNA - drug effects</topic><topic>DNA - metabolism</topic><topic>DNA Adducts</topic><topic>DNA Damage</topic><topic>DNA damage and repair</topic><topic>DNA REPAIR</topic><topic>DNA Repair - radiation effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>DOSE-RESPONSE RELATIONSHIPS</topic><topic>DOSES</topic><topic>Drug resistance</topic><topic>Drug Resistance - radiation effects</topic><topic>DRUGS</topic><topic>ENZYMES</topic><topic>FRACTIONATED IRRADIATION</topic><topic>Genital system. Mammary gland</topic><topic>GLUTATHIONE</topic><topic>Glutathione - metabolism</topic><topic>Glutathione Peroxidase - metabolism</topic><topic>Glutathione Reductase - metabolism</topic><topic>Glutathione Transferase - metabolism</topic><topic>GONADS</topic><topic>Humans</topic><topic>IN VITRO</topic><topic>IRRADIATION</topic><topic>Male</topic><topic>MALE GENITALS</topic><topic>MAMMALS</topic><topic>MAN</topic><topic>Medical sciences</topic><topic>NEOPLASMS</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANS</topic><topic>OXIDOREDUCTASES</topic><topic>PEPTIDES</topic><topic>PEROXIDASES</topic><topic>POLYPEPTIDES</topic><topic>PRIMATES</topic><topic>PROTEINS</topic><topic>Radiation</topic><topic>RADIATION DOSES</topic><topic>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</topic><topic>RADIOPROTECTIVE SUBSTANCES</topic><topic>RADIOSENSITIVITY</topic><topic>Radiotherapy Dosage</topic><topic>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</topic><topic>RECOVERY</topic><topic>REPAIR</topic><topic>Teratoma - enzymology</topic><topic>Teratoma - metabolism</topic><topic>Teratoma - pathology</topic><topic>TESTES</topic><topic>Testicular Neoplasms - enzymology</topic><topic>Testicular Neoplasms - metabolism</topic><topic>Testicular Neoplasms - pathology</topic><topic>Time Factors</topic><topic>TRANSFERASES</topic><topic>TUMOR CELLS</topic><topic>Tumor Cells, Cultured - enzymology</topic><topic>Tumor Cells, Cultured - radiation effects</topic><topic>VERTEBRATES 560120 -- Radiation Effects on Biochemicals, Cells, &amp; Tissue Culture</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hill, Bridget T.</creatorcontrib><creatorcontrib>Shellard, Sharon A.</creatorcontrib><creatorcontrib>Hosking, Louise K.</creatorcontrib><creatorcontrib>Fichtinger-Schepman, Anne Marie J.</creatorcontrib><creatorcontrib>Bedford, Philip</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>OSTI.GOV</collection><jtitle>International journal of radiation oncology, biology, physics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hill, Bridget T.</au><au>Shellard, Sharon A.</au><au>Hosking, Louise K.</au><au>Fichtinger-Schepman, Anne Marie J.</au><au>Bedford, Philip</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhanced dna repair and tolerance of DNA damage associated with resistance to cis-diammine-dichloroplatinum (II) after in vitro exposure of a human teratoma cell line to fractionated X-irradiation</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>1990-07</date><risdate>1990</risdate><volume>19</volume><issue>1</issue><spage>75</spage><epage>83</epage><pages>75-83</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><coden>IOBPD3</coden><abstract>In vitro exposure of a human testicular teratoma continuous cell line to fractionated X-irradiation resulted in the expression of resistance to cisplatin. In two independently-derived sublines, designated SUSA-DXR 3 and SUSADXR 10 resulting from treatment with either 13 fractions of 1.5 Gy (dose required to reduce survival by 1 log) or 10 fractions of 3 Gy (dose required to reduce survival by 2 logs) respectivves, the IC 50 values for cisplatin were 2− and 3.1-fold higher than that of the parental cell line. These sublines were cross-resistant to carboplatin (approximately 2-fold) but not to adriamycin and they showed unaltered radiosensitivities. The SUSA-DXR 10 subline expressed some cross-resistance to mitomycin C and melphalan but none to Carmustine (BCNU). Total glutathione content was significantly reduced in both SUSA-DXR 10 and SUSA-DXR 13 cells, but the activities of associated enzymes, including the glutathione S-transferases, peroxidase and reductase were not modified significantly in the resistant sublines. Resistance in the SUSA-DXR 10 subline was associated with significantly decreased 195mcisplatin uptake (p &lt; 0.01), but this was not reflected in a reduced level of drug bound to the DNA. The formation and removal of four platinum DNA adducts were immunochemically quantitated. Immediately following drug treatment there was a higher level of total platination of the DNA in the resistant subline indicative of increased tolerance to DNA damage. After an 18 hr post treatment incubation, there was an indication of some repair capacity in this SUSA-DXR 10 cell line, which was not apparent in the parental cells. Neither the parental nor the SUSA-DXR 10 cell line was proficient in the repair of the major adduct Pt-GG, whereas both lines repaired the monofunctional adduct and the adduct Pt(GMP) 2. SUSA-DXR 10 cells were also able to repair the intrastrand adduct Pt-AG and interstrand crosslinks, unlike the repair deficient parental cells. Higher levels of interstrand crosslinks were characteristic of the SUSA-DXR 10 subline. These observations therefore implicate both enhanced repair and increased tolerance of DNA damage as mechanisms of resistance to cisplatin resulting from in vitro exposure of a human teratoma cell line to fractionated X-irradiation.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>2380098</pmid><doi>10.1016/0360-3016(90)90137-9</doi><tpages>9</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0360-3016
ispartof International journal of radiation oncology, biology, physics, 1990-07, Vol.19 (1), p.75-83
issn 0360-3016
1879-355X
language eng
recordid cdi_osti_scitechconnect_6616416
source MEDLINE; ScienceDirect Journals (5 years ago - present)
subjects ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
Biological and medical sciences
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
Cisplatin
Cisplatin - metabolism
Cisplatin - pharmacokinetics
Cisplatin - pharmacology
DISEASES
DNA - drug effects
DNA - metabolism
DNA Adducts
DNA Damage
DNA damage and repair
DNA REPAIR
DNA Repair - radiation effects
Dose-Response Relationship, Drug
DOSE-RESPONSE RELATIONSHIPS
DOSES
Drug resistance
Drug Resistance - radiation effects
DRUGS
ENZYMES
FRACTIONATED IRRADIATION
Genital system. Mammary gland
GLUTATHIONE
Glutathione - metabolism
Glutathione Peroxidase - metabolism
Glutathione Reductase - metabolism
Glutathione Transferase - metabolism
GONADS
Humans
IN VITRO
IRRADIATION
Male
MALE GENITALS
MAMMALS
MAN
Medical sciences
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PEPTIDES
PEROXIDASES
POLYPEPTIDES
PRIMATES
PROTEINS
Radiation
RADIATION DOSES
RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY
Radiotherapy Dosage
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
RECOVERY
REPAIR
Teratoma - enzymology
Teratoma - metabolism
Teratoma - pathology
TESTES
Testicular Neoplasms - enzymology
Testicular Neoplasms - metabolism
Testicular Neoplasms - pathology
Time Factors
TRANSFERASES
TUMOR CELLS
Tumor Cells, Cultured - enzymology
Tumor Cells, Cultured - radiation effects
VERTEBRATES 560120 -- Radiation Effects on Biochemicals, Cells, & Tissue Culture
title Enhanced dna repair and tolerance of DNA damage associated with resistance to cis-diammine-dichloroplatinum (II) after in vitro exposure of a human teratoma cell line to fractionated X-irradiation
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