Monitoring genotoxicity in patients receiving chemotherapy for cancer: application of the PIG-A assay
•A human PIG-A assay was conducted.•The human PIG-A assay allows minimally invasive human genotoxic monitoring.•Blood samples collected from patients with cancer receiving chemotherapy were analyzed.•The human PIG-A assay could detect strong chemotherapy-induced genotoxicity.•The human PIG-A assay c...
Gespeichert in:
| Veröffentlicht in: | Mutation research. Genetic toxicology and environmental mutagenesis 2016-09, Vol.808, p.20-26 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 26 |
|---|---|
| container_issue | |
| container_start_page | 20 |
| container_title | Mutation research. Genetic toxicology and environmental mutagenesis |
| container_volume | 808 |
| creator | Horibata, Katsuyoshi Ukai, Akiko Ishikawa, Shigeo Sugano, Ayako Honma, Masamitsu |
| description | •A human PIG-A assay was conducted.•The human PIG-A assay allows minimally invasive human genotoxic monitoring.•Blood samples collected from patients with cancer receiving chemotherapy were analyzed.•The human PIG-A assay could detect strong chemotherapy-induced genotoxicity.•The human PIG-A assay could detect cumulative genotoxicity.
The recently introduced Pig-a in vivo gene mutation assay measures endogeneous mutations of Pig-a (human, PIG-A), an X-linked gene that is conserved across species from rodents to humans. Flow cytometric analysis enables the enumeration of glycosylphosphatidylinositol (GPI) anchor-deficient erythrocytes, resulting from a mutation in Pig-a/PIG-A, in only a few microliters of peripheral blood. Pig-a/PIG-A mutations appear to function in a neutral manner, allowing evaluation of the accumulated genotoxic effects of repeated exposures. To date, most Pig-a studies have been conducted in rodents; only a few reports regarding human applications of the PIG-A assay have been published. We have conducted a PIG-A assay in the context of human genotoxicity monitoring. Peripheral blood was collected from healthy human donors and chemotherapy-treated cancer patients at Yamagata University Hospital. To investigate the PIG-A mutant frequency (MF) induced by chemotherapy, red blood cells were analyzed via flow cytometry following staining with allophycocyanin-conjugated anti-CD235ab (erythrocyte specific) and fluorescein isothiocyanate-conjugated anti-CD59 antibodies (GPI-anchored protein specific). Reticulocyte frequencies (%RET) were also analyzed using a phycoerythrin-conjugated anti-CD71 antibody to monitor bone marrow suppression and reticulocytosis. Two of 27 patients exhibited a significantly elevated frequency of PIG-A mutants. Although we observed either a reduced or an increased %RET in all patients, no association was observed between this factor and the PIG-A MF. Unfortunately, we could not analyze blood samples collected before treatment during therapeutic processes. Additionally, the sampling time point for some patients was too short to express the PIG-A mutant phenotypes. Therefore, the possibility of natively high PIG-A MFs prior to treatment must be considered. The human PIG-A assay shows promise as a human genotoxicity monitoring method. |
| doi_str_mv | 10.1016/j.mrgentox.2016.08.002 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1827915320</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1383571816301589</els_id><sourcerecordid>4199213671</sourcerecordid><originalsourceid>FETCH-LOGICAL-c429t-be18e65bb8cabd7cb0ab775ff9181c60d250ea8441f5780653abaf31587371f03</originalsourceid><addsrcrecordid>eNqNkcFu1DAURS0EomXgFypLbNgkPNtx7LCiqqCtVAQLWFuO89x6NImDnak6f4-jaVl0Ayvb0rn36fkQcsagZsDaj9t6TLc4LfGh5uVdg64B-AtyyrTqKiE7_rLchRaVVEyfkDc5bwsAAvRrcsJVK1Sj-SnBb3EKS0xhuqWlL5bC4MJyoGGis11CGZFpQofhfkXcHY5xucNk5wP1MVFnJ4fpE7XzvAuuBOJEo6cFoT-uL6tzanO2h7fklbe7jO8ezw359fXLz4ur6ub75fXF-U3lGt4tVY9MYyv7XjvbD8r1YHulpPcd08y1MHAJaHXTMC-VhlYK21svmNRKKOZBbMiHY--c4u895sWMITvc7eyEcZ8N01x1TAr-Xyi0wFd6Q94_Q7dxn6ayyEo1kkkJulDtkXIp5pzQmzmF0aaDYWBWZ2ZrnpyZ1ZkBbYqSEjx7rN_3Iw5_Y0-SCvD5CGD5uvuAyWRXxDgcQjGzmCGGf834A5niq6U</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1824515508</pqid></control><display><type>article</type><title>Monitoring genotoxicity in patients receiving chemotherapy for cancer: application of the PIG-A assay</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Horibata, Katsuyoshi ; Ukai, Akiko ; Ishikawa, Shigeo ; Sugano, Ayako ; Honma, Masamitsu</creator><creatorcontrib>Horibata, Katsuyoshi ; Ukai, Akiko ; Ishikawa, Shigeo ; Sugano, Ayako ; Honma, Masamitsu</creatorcontrib><description>•A human PIG-A assay was conducted.•The human PIG-A assay allows minimally invasive human genotoxic monitoring.•Blood samples collected from patients with cancer receiving chemotherapy were analyzed.•The human PIG-A assay could detect strong chemotherapy-induced genotoxicity.•The human PIG-A assay could detect cumulative genotoxicity.
The recently introduced Pig-a in vivo gene mutation assay measures endogeneous mutations of Pig-a (human, PIG-A), an X-linked gene that is conserved across species from rodents to humans. Flow cytometric analysis enables the enumeration of glycosylphosphatidylinositol (GPI) anchor-deficient erythrocytes, resulting from a mutation in Pig-a/PIG-A, in only a few microliters of peripheral blood. Pig-a/PIG-A mutations appear to function in a neutral manner, allowing evaluation of the accumulated genotoxic effects of repeated exposures. To date, most Pig-a studies have been conducted in rodents; only a few reports regarding human applications of the PIG-A assay have been published. We have conducted a PIG-A assay in the context of human genotoxicity monitoring. Peripheral blood was collected from healthy human donors and chemotherapy-treated cancer patients at Yamagata University Hospital. To investigate the PIG-A mutant frequency (MF) induced by chemotherapy, red blood cells were analyzed via flow cytometry following staining with allophycocyanin-conjugated anti-CD235ab (erythrocyte specific) and fluorescein isothiocyanate-conjugated anti-CD59 antibodies (GPI-anchored protein specific). Reticulocyte frequencies (%RET) were also analyzed using a phycoerythrin-conjugated anti-CD71 antibody to monitor bone marrow suppression and reticulocytosis. Two of 27 patients exhibited a significantly elevated frequency of PIG-A mutants. Although we observed either a reduced or an increased %RET in all patients, no association was observed between this factor and the PIG-A MF. Unfortunately, we could not analyze blood samples collected before treatment during therapeutic processes. Additionally, the sampling time point for some patients was too short to express the PIG-A mutant phenotypes. Therefore, the possibility of natively high PIG-A MFs prior to treatment must be considered. The human PIG-A assay shows promise as a human genotoxicity monitoring method.</description><identifier>ISSN: 1383-5718</identifier><identifier>EISSN: 1879-3592</identifier><identifier>DOI: 10.1016/j.mrgentox.2016.08.002</identifier><identifier>PMID: 27637482</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - therapeutic use ; Cancer ; Chemotherapy ; Erythrocytes - drug effects ; Female ; Genetics ; Genotoxicity ; Glycosylphosphatidylinositol anchor ; Humans ; Male ; Membrane Proteins - genetics ; Middle Aged ; Mutagenicity Tests - methods ; Mutation ; Mutation Rate ; Neoplasms - drug therapy ; Red blood cell ; Reticulocytes - drug effects ; Sampling ; Toxicity</subject><ispartof>Mutation research. Genetic toxicology and environmental mutagenesis, 2016-09, Vol.808, p.20-26</ispartof><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV Sep 15, 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-be18e65bb8cabd7cb0ab775ff9181c60d250ea8441f5780653abaf31587371f03</citedby><cites>FETCH-LOGICAL-c429t-be18e65bb8cabd7cb0ab775ff9181c60d250ea8441f5780653abaf31587371f03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1383571816301589$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27637482$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Horibata, Katsuyoshi</creatorcontrib><creatorcontrib>Ukai, Akiko</creatorcontrib><creatorcontrib>Ishikawa, Shigeo</creatorcontrib><creatorcontrib>Sugano, Ayako</creatorcontrib><creatorcontrib>Honma, Masamitsu</creatorcontrib><title>Monitoring genotoxicity in patients receiving chemotherapy for cancer: application of the PIG-A assay</title><title>Mutation research. Genetic toxicology and environmental mutagenesis</title><addtitle>Mutat Res Genet Toxicol Environ Mutagen</addtitle><description>•A human PIG-A assay was conducted.•The human PIG-A assay allows minimally invasive human genotoxic monitoring.•Blood samples collected from patients with cancer receiving chemotherapy were analyzed.•The human PIG-A assay could detect strong chemotherapy-induced genotoxicity.•The human PIG-A assay could detect cumulative genotoxicity.
The recently introduced Pig-a in vivo gene mutation assay measures endogeneous mutations of Pig-a (human, PIG-A), an X-linked gene that is conserved across species from rodents to humans. Flow cytometric analysis enables the enumeration of glycosylphosphatidylinositol (GPI) anchor-deficient erythrocytes, resulting from a mutation in Pig-a/PIG-A, in only a few microliters of peripheral blood. Pig-a/PIG-A mutations appear to function in a neutral manner, allowing evaluation of the accumulated genotoxic effects of repeated exposures. To date, most Pig-a studies have been conducted in rodents; only a few reports regarding human applications of the PIG-A assay have been published. We have conducted a PIG-A assay in the context of human genotoxicity monitoring. Peripheral blood was collected from healthy human donors and chemotherapy-treated cancer patients at Yamagata University Hospital. To investigate the PIG-A mutant frequency (MF) induced by chemotherapy, red blood cells were analyzed via flow cytometry following staining with allophycocyanin-conjugated anti-CD235ab (erythrocyte specific) and fluorescein isothiocyanate-conjugated anti-CD59 antibodies (GPI-anchored protein specific). Reticulocyte frequencies (%RET) were also analyzed using a phycoerythrin-conjugated anti-CD71 antibody to monitor bone marrow suppression and reticulocytosis. Two of 27 patients exhibited a significantly elevated frequency of PIG-A mutants. Although we observed either a reduced or an increased %RET in all patients, no association was observed between this factor and the PIG-A MF. Unfortunately, we could not analyze blood samples collected before treatment during therapeutic processes. Additionally, the sampling time point for some patients was too short to express the PIG-A mutant phenotypes. Therefore, the possibility of natively high PIG-A MFs prior to treatment must be considered. The human PIG-A assay shows promise as a human genotoxicity monitoring method.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Cancer</subject><subject>Chemotherapy</subject><subject>Erythrocytes - drug effects</subject><subject>Female</subject><subject>Genetics</subject><subject>Genotoxicity</subject><subject>Glycosylphosphatidylinositol anchor</subject><subject>Humans</subject><subject>Male</subject><subject>Membrane Proteins - genetics</subject><subject>Middle Aged</subject><subject>Mutagenicity Tests - methods</subject><subject>Mutation</subject><subject>Mutation Rate</subject><subject>Neoplasms - drug therapy</subject><subject>Red blood cell</subject><subject>Reticulocytes - drug effects</subject><subject>Sampling</subject><subject>Toxicity</subject><issn>1383-5718</issn><issn>1879-3592</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFu1DAURS0EomXgFypLbNgkPNtx7LCiqqCtVAQLWFuO89x6NImDnak6f4-jaVl0Ayvb0rn36fkQcsagZsDaj9t6TLc4LfGh5uVdg64B-AtyyrTqKiE7_rLchRaVVEyfkDc5bwsAAvRrcsJVK1Sj-SnBb3EKS0xhuqWlL5bC4MJyoGGis11CGZFpQofhfkXcHY5xucNk5wP1MVFnJ4fpE7XzvAuuBOJEo6cFoT-uL6tzanO2h7fklbe7jO8ezw359fXLz4ur6ub75fXF-U3lGt4tVY9MYyv7XjvbD8r1YHulpPcd08y1MHAJaHXTMC-VhlYK21svmNRKKOZBbMiHY--c4u895sWMITvc7eyEcZ8N01x1TAr-Xyi0wFd6Q94_Q7dxn6ayyEo1kkkJulDtkXIp5pzQmzmF0aaDYWBWZ2ZrnpyZ1ZkBbYqSEjx7rN_3Iw5_Y0-SCvD5CGD5uvuAyWRXxDgcQjGzmCGGf834A5niq6U</recordid><startdate>20160915</startdate><enddate>20160915</enddate><creator>Horibata, Katsuyoshi</creator><creator>Ukai, Akiko</creator><creator>Ishikawa, Shigeo</creator><creator>Sugano, Ayako</creator><creator>Honma, Masamitsu</creator><general>Elsevier B.V</general><general>Elsevier BV</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>7ST</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>SOI</scope><scope>7X8</scope></search><sort><creationdate>20160915</creationdate><title>Monitoring genotoxicity in patients receiving chemotherapy for cancer: application of the PIG-A assay</title><author>Horibata, Katsuyoshi ; Ukai, Akiko ; Ishikawa, Shigeo ; Sugano, Ayako ; Honma, Masamitsu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-be18e65bb8cabd7cb0ab775ff9181c60d250ea8441f5780653abaf31587371f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Cancer</topic><topic>Chemotherapy</topic><topic>Erythrocytes - drug effects</topic><topic>Female</topic><topic>Genetics</topic><topic>Genotoxicity</topic><topic>Glycosylphosphatidylinositol anchor</topic><topic>Humans</topic><topic>Male</topic><topic>Membrane Proteins - genetics</topic><topic>Middle Aged</topic><topic>Mutagenicity Tests - methods</topic><topic>Mutation</topic><topic>Mutation Rate</topic><topic>Neoplasms - drug therapy</topic><topic>Red blood cell</topic><topic>Reticulocytes - drug effects</topic><topic>Sampling</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Horibata, Katsuyoshi</creatorcontrib><creatorcontrib>Ukai, Akiko</creatorcontrib><creatorcontrib>Ishikawa, Shigeo</creatorcontrib><creatorcontrib>Sugano, Ayako</creatorcontrib><creatorcontrib>Honma, Masamitsu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Mutation research. Genetic toxicology and environmental mutagenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Horibata, Katsuyoshi</au><au>Ukai, Akiko</au><au>Ishikawa, Shigeo</au><au>Sugano, Ayako</au><au>Honma, Masamitsu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Monitoring genotoxicity in patients receiving chemotherapy for cancer: application of the PIG-A assay</atitle><jtitle>Mutation research. Genetic toxicology and environmental mutagenesis</jtitle><addtitle>Mutat Res Genet Toxicol Environ Mutagen</addtitle><date>2016-09-15</date><risdate>2016</risdate><volume>808</volume><spage>20</spage><epage>26</epage><pages>20-26</pages><issn>1383-5718</issn><eissn>1879-3592</eissn><abstract>•A human PIG-A assay was conducted.•The human PIG-A assay allows minimally invasive human genotoxic monitoring.•Blood samples collected from patients with cancer receiving chemotherapy were analyzed.•The human PIG-A assay could detect strong chemotherapy-induced genotoxicity.•The human PIG-A assay could detect cumulative genotoxicity.
The recently introduced Pig-a in vivo gene mutation assay measures endogeneous mutations of Pig-a (human, PIG-A), an X-linked gene that is conserved across species from rodents to humans. Flow cytometric analysis enables the enumeration of glycosylphosphatidylinositol (GPI) anchor-deficient erythrocytes, resulting from a mutation in Pig-a/PIG-A, in only a few microliters of peripheral blood. Pig-a/PIG-A mutations appear to function in a neutral manner, allowing evaluation of the accumulated genotoxic effects of repeated exposures. To date, most Pig-a studies have been conducted in rodents; only a few reports regarding human applications of the PIG-A assay have been published. We have conducted a PIG-A assay in the context of human genotoxicity monitoring. Peripheral blood was collected from healthy human donors and chemotherapy-treated cancer patients at Yamagata University Hospital. To investigate the PIG-A mutant frequency (MF) induced by chemotherapy, red blood cells were analyzed via flow cytometry following staining with allophycocyanin-conjugated anti-CD235ab (erythrocyte specific) and fluorescein isothiocyanate-conjugated anti-CD59 antibodies (GPI-anchored protein specific). Reticulocyte frequencies (%RET) were also analyzed using a phycoerythrin-conjugated anti-CD71 antibody to monitor bone marrow suppression and reticulocytosis. Two of 27 patients exhibited a significantly elevated frequency of PIG-A mutants. Although we observed either a reduced or an increased %RET in all patients, no association was observed between this factor and the PIG-A MF. Unfortunately, we could not analyze blood samples collected before treatment during therapeutic processes. Additionally, the sampling time point for some patients was too short to express the PIG-A mutant phenotypes. Therefore, the possibility of natively high PIG-A MFs prior to treatment must be considered. The human PIG-A assay shows promise as a human genotoxicity monitoring method.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27637482</pmid><doi>10.1016/j.mrgentox.2016.08.002</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1383-5718 |
| ispartof | Mutation research. Genetic toxicology and environmental mutagenesis, 2016-09, Vol.808, p.20-26 |
| issn | 1383-5718 1879-3592 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1827915320 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Aged Aged, 80 and over Antineoplastic Agents - adverse effects Antineoplastic Agents - therapeutic use Cancer Chemotherapy Erythrocytes - drug effects Female Genetics Genotoxicity Glycosylphosphatidylinositol anchor Humans Male Membrane Proteins - genetics Middle Aged Mutagenicity Tests - methods Mutation Mutation Rate Neoplasms - drug therapy Red blood cell Reticulocytes - drug effects Sampling Toxicity |
| title | Monitoring genotoxicity in patients receiving chemotherapy for cancer: application of the PIG-A assay |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T22%3A47%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Monitoring%20genotoxicity%20in%20patients%20receiving%20chemotherapy%20for%20cancer:%20application%20of%20the%20PIG-A%20assay&rft.jtitle=Mutation%20research.%20Genetic%20toxicology%20and%20environmental%20mutagenesis&rft.au=Horibata,%20Katsuyoshi&rft.date=2016-09-15&rft.volume=808&rft.spage=20&rft.epage=26&rft.pages=20-26&rft.issn=1383-5718&rft.eissn=1879-3592&rft_id=info:doi/10.1016/j.mrgentox.2016.08.002&rft_dat=%3Cproquest_cross%3E4199213671%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1824515508&rft_id=info:pmid/27637482&rft_els_id=S1383571816301589&rfr_iscdi=true |