Erythrocyte PIG‐A mutant frequencies in cancer patients receiving cisplatin
Abstract Background Cisplatin is a primary chemotherapy choice for various solid tumors. DNA damage caused by cisplatin results in apoptosis of tumor cells. Cisplatin‐induced DNA damage, however, may also result in mutations in normal cells and the initiation of secondary malignancies. In the curren...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.6895 |
| _version_ | 1797216968109981696 |
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| author | Vasily N. Dobrovolsky Omar T. Atiq Robert H. Heflich Mackean Maisha Page B. McKinzie Mason G. Pearce Timothy W. Robison |
| author_facet | Vasily N. Dobrovolsky Omar T. Atiq Robert H. Heflich Mackean Maisha Page B. McKinzie Mason G. Pearce Timothy W. Robison |
| author_sort | Vasily N. Dobrovolsky |
| collection | DOAJ |
| description | Abstract Background Cisplatin is a primary chemotherapy choice for various solid tumors. DNA damage caused by cisplatin results in apoptosis of tumor cells. Cisplatin‐induced DNA damage, however, may also result in mutations in normal cells and the initiation of secondary malignancies. In the current study, we have used the erythrocyte PIG‐A assay to evaluate mutagenesis in non‐tumor hematopoietic tissue of cancer patients receiving cisplatin chemotherapy. Methods Twenty‐one head and neck cancer patients undergoing treatment with cisplatin were monitored for the presence of PIG‐A mutant total erythrocytes and the young erythrocytes, reticulocytes (RETs), in peripheral blood for up to five and a half months from the initiation of the anti‐neoplastic chemotherapy. Results PIG‐A mutant frequency (MF) in RETs increased at least two‐fold in 15 patients at some point of the monitoring, while the frequency of total mutant RBCs increased at least two‐fold in 6 patients. A general trend for an increase in the frequency of mutant RETs and total mutant RBCs was observed in 19 and 18 patients, respectively. Only in one patient did both RET and total RBC PIG‐A MFs did not increase at any time‐point over the monitoring period. Conclusion Cisplatin chemotherapy induces moderate increases in the frequency of PIG‐A mutant erythrocytes in head and neck cancer patients. Mutagenicity measured with the flow cytometric PIG‐A assay may serve as a tool for predicting adverse outcomes of genotoxic antineoplastic therapy. |
| first_indexed | 2024-03-07T15:43:31Z |
| format | Article |
| id | doaj.art-54556bcd1c1047a09ad9e26bf3756514 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-24T11:54:23Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-54556bcd1c1047a09ad9e26bf37565142024-04-09T05:45:47ZengWileyCancer Medicine2045-76342024-02-01133n/an/a10.1002/cam4.6895Erythrocyte PIG‐A mutant frequencies in cancer patients receiving cisplatinVasily N. Dobrovolsky0Omar T. Atiq1Robert H. Heflich2Mackean Maisha3Page B. McKinzie4Mason G. Pearce5Timothy W. Robison6Division of Genetic and Molecular Toxicology National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA) Jefferson Arkansas USAUniversity of Arkansas for Medical Sciences (UAMS) Winthrop P. Rockefeller Cancer Institute Little Rock Arkansas USADivision of Genetic and Molecular Toxicology National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA) Jefferson Arkansas USAOffice of Scientific Coordination, NCTR, FDA Jefferson Arkansas USADivision of Genetic and Molecular Toxicology National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA) Jefferson Arkansas USADivision of Genetic and Molecular Toxicology National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA) Jefferson Arkansas USAOffice of New Drugs, OII, DPTII, Center for Drug Evaluation and Research (CDER), US FDA Silver Spring Maryland USAAbstract Background Cisplatin is a primary chemotherapy choice for various solid tumors. DNA damage caused by cisplatin results in apoptosis of tumor cells. Cisplatin‐induced DNA damage, however, may also result in mutations in normal cells and the initiation of secondary malignancies. In the current study, we have used the erythrocyte PIG‐A assay to evaluate mutagenesis in non‐tumor hematopoietic tissue of cancer patients receiving cisplatin chemotherapy. Methods Twenty‐one head and neck cancer patients undergoing treatment with cisplatin were monitored for the presence of PIG‐A mutant total erythrocytes and the young erythrocytes, reticulocytes (RETs), in peripheral blood for up to five and a half months from the initiation of the anti‐neoplastic chemotherapy. Results PIG‐A mutant frequency (MF) in RETs increased at least two‐fold in 15 patients at some point of the monitoring, while the frequency of total mutant RBCs increased at least two‐fold in 6 patients. A general trend for an increase in the frequency of mutant RETs and total mutant RBCs was observed in 19 and 18 patients, respectively. Only in one patient did both RET and total RBC PIG‐A MFs did not increase at any time‐point over the monitoring period. Conclusion Cisplatin chemotherapy induces moderate increases in the frequency of PIG‐A mutant erythrocytes in head and neck cancer patients. Mutagenicity measured with the flow cytometric PIG‐A assay may serve as a tool for predicting adverse outcomes of genotoxic antineoplastic therapy.https://doi.org/10.1002/cam4.6895chemotherapyerythrocyteshead and neck cancer (HNC)mutationsPhosphatidylinositol glycan class‐A (PIG‐A) gene |
| spellingShingle | Vasily N. Dobrovolsky Omar T. Atiq Robert H. Heflich Mackean Maisha Page B. McKinzie Mason G. Pearce Timothy W. Robison Erythrocyte PIG‐A mutant frequencies in cancer patients receiving cisplatin Cancer Medicine chemotherapy erythrocytes head and neck cancer (HNC) mutations Phosphatidylinositol glycan class‐A (PIG‐A) gene |
| title | Erythrocyte PIG‐A mutant frequencies in cancer patients receiving cisplatin |
| title_full | Erythrocyte PIG‐A mutant frequencies in cancer patients receiving cisplatin |
| title_fullStr | Erythrocyte PIG‐A mutant frequencies in cancer patients receiving cisplatin |
| title_full_unstemmed | Erythrocyte PIG‐A mutant frequencies in cancer patients receiving cisplatin |
| title_short | Erythrocyte PIG‐A mutant frequencies in cancer patients receiving cisplatin |
| title_sort | erythrocyte pig a mutant frequencies in cancer patients receiving cisplatin |
| topic | chemotherapy erythrocytes head and neck cancer (HNC) mutations Phosphatidylinositol glycan class‐A (PIG‐A) gene |
| url | https://doi.org/10.1002/cam4.6895 |
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