Cisplatin Reduces the Frequencies of Radiotherapy-Induced Micronuclei in Peripheral Blood Lymphocytes of Patients with Gynaecological Cancer: Possible Implications for the Risk of Second Malignant Neoplasms
Gynaecologic cancers are common among women and treatment includes surgery, radiotherapy or chemotherapy, where the last two methods induce DNA damage in non-targeted cells like peripheral blood lymphocytes (PBL). Damaged normal cells can transform leading to second malignant neoplasms (SMN) but the...
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MDPI AG
2021-10-01
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| author | Aneta Węgierek-Ciuk Anna Lankoff Halina Lisowska Piotr Kędzierawski Pamela Akuwudike Lovisa Lundholm Andrzej Wojcik |
| author_facet | Aneta Węgierek-Ciuk Anna Lankoff Halina Lisowska Piotr Kędzierawski Pamela Akuwudike Lovisa Lundholm Andrzej Wojcik |
| author_sort | Aneta Węgierek-Ciuk |
| collection | DOAJ |
| description | Gynaecologic cancers are common among women and treatment includes surgery, radiotherapy or chemotherapy, where the last two methods induce DNA damage in non-targeted cells like peripheral blood lymphocytes (PBL). Damaged normal cells can transform leading to second malignant neoplasms (SMN) but the level of risk and impact of risk modifiers is not well defined. We investigated how radiotherapy alone or in combination with chemotherapy induce DNA damage in PBL of cervix and endometrial cancer patients during therapy. Blood samples were collected from nine endometrial cancer patients (treatment with radiotherapy + chemotherapy—RC) and nine cervical cancer patients (treatment with radiotherapy alone—R) before radiotherapy, 3 weeks after onset of radiotherapy and at the end of radiotherapy. Half of each blood sample was irradiated ex vivo with 2 Gy of gamma radiation in order to check how therapy influenced the sensitivity of PBL to radiation. Analysed endpoints were micronucleus (MN) frequencies, apoptosis frequencies and cell proliferation index. The results were characterised by strong individual variation, especially the MN frequencies and proliferation index. On average, despite higher total dose and larger fields, therapy alone induced the same level of MN in PBL of RC patients as compared to R. This result was accompanied by a higher level of apoptosis and stronger inhibition of cell proliferation in RC patients. The ex vivo dose induced fewer MN, more apoptosis and more strongly inhibited proliferation of PBL of RC as compared to R patients. These results are interpreted as evidence for a sensitizing effect of chemotherapy on radiation cytotoxicity. The possible implications for the risk of second malignant neoplasms are discussed. |
| first_indexed | 2024-03-10T06:40:01Z |
| format | Article |
| id | doaj.art-f2d8740c4430432d8ba522c714f74062 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:40:01Z |
| publishDate | 2021-10-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-f2d8740c4430432d8ba522c714f740622023-11-22T17:47:52ZengMDPI AGCells2073-44092021-10-011010270910.3390/cells10102709Cisplatin Reduces the Frequencies of Radiotherapy-Induced Micronuclei in Peripheral Blood Lymphocytes of Patients with Gynaecological Cancer: Possible Implications for the Risk of Second Malignant NeoplasmsAneta Węgierek-Ciuk0Anna Lankoff1Halina Lisowska2Piotr Kędzierawski3Pamela Akuwudike4Lovisa Lundholm5Andrzej Wojcik6Department of Medical Biology, Institute of Biology, Jan Kochanowski University, Uniwersytecka 7, 25-406 Kielce, PolandDepartment of Medical Biology, Institute of Biology, Jan Kochanowski University, Uniwersytecka 7, 25-406 Kielce, PolandDepartment of Medical Biology, Institute of Biology, Jan Kochanowski University, Uniwersytecka 7, 25-406 Kielce, PolandDepartment of Radiotherapy, Holy Cross Cancer Center, Artwinskiego 3, 25-734 Kielce, PolandCentre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, SwedenCentre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, SwedenDepartment of Medical Biology, Institute of Biology, Jan Kochanowski University, Uniwersytecka 7, 25-406 Kielce, PolandGynaecologic cancers are common among women and treatment includes surgery, radiotherapy or chemotherapy, where the last two methods induce DNA damage in non-targeted cells like peripheral blood lymphocytes (PBL). Damaged normal cells can transform leading to second malignant neoplasms (SMN) but the level of risk and impact of risk modifiers is not well defined. We investigated how radiotherapy alone or in combination with chemotherapy induce DNA damage in PBL of cervix and endometrial cancer patients during therapy. Blood samples were collected from nine endometrial cancer patients (treatment with radiotherapy + chemotherapy—RC) and nine cervical cancer patients (treatment with radiotherapy alone—R) before radiotherapy, 3 weeks after onset of radiotherapy and at the end of radiotherapy. Half of each blood sample was irradiated ex vivo with 2 Gy of gamma radiation in order to check how therapy influenced the sensitivity of PBL to radiation. Analysed endpoints were micronucleus (MN) frequencies, apoptosis frequencies and cell proliferation index. The results were characterised by strong individual variation, especially the MN frequencies and proliferation index. On average, despite higher total dose and larger fields, therapy alone induced the same level of MN in PBL of RC patients as compared to R. This result was accompanied by a higher level of apoptosis and stronger inhibition of cell proliferation in RC patients. The ex vivo dose induced fewer MN, more apoptosis and more strongly inhibited proliferation of PBL of RC as compared to R patients. These results are interpreted as evidence for a sensitizing effect of chemotherapy on radiation cytotoxicity. The possible implications for the risk of second malignant neoplasms are discussed.https://www.mdpi.com/2073-4409/10/10/2709radiotherapychemotherapychromosomal damageapoptosissecond primary cancerssecond malignant neoplasms |
| spellingShingle | Aneta Węgierek-Ciuk Anna Lankoff Halina Lisowska Piotr Kędzierawski Pamela Akuwudike Lovisa Lundholm Andrzej Wojcik Cisplatin Reduces the Frequencies of Radiotherapy-Induced Micronuclei in Peripheral Blood Lymphocytes of Patients with Gynaecological Cancer: Possible Implications for the Risk of Second Malignant Neoplasms Cells radiotherapy chemotherapy chromosomal damage apoptosis second primary cancers second malignant neoplasms |
| title | Cisplatin Reduces the Frequencies of Radiotherapy-Induced Micronuclei in Peripheral Blood Lymphocytes of Patients with Gynaecological Cancer: Possible Implications for the Risk of Second Malignant Neoplasms |
| title_full | Cisplatin Reduces the Frequencies of Radiotherapy-Induced Micronuclei in Peripheral Blood Lymphocytes of Patients with Gynaecological Cancer: Possible Implications for the Risk of Second Malignant Neoplasms |
| title_fullStr | Cisplatin Reduces the Frequencies of Radiotherapy-Induced Micronuclei in Peripheral Blood Lymphocytes of Patients with Gynaecological Cancer: Possible Implications for the Risk of Second Malignant Neoplasms |
| title_full_unstemmed | Cisplatin Reduces the Frequencies of Radiotherapy-Induced Micronuclei in Peripheral Blood Lymphocytes of Patients with Gynaecological Cancer: Possible Implications for the Risk of Second Malignant Neoplasms |
| title_short | Cisplatin Reduces the Frequencies of Radiotherapy-Induced Micronuclei in Peripheral Blood Lymphocytes of Patients with Gynaecological Cancer: Possible Implications for the Risk of Second Malignant Neoplasms |
| title_sort | cisplatin reduces the frequencies of radiotherapy induced micronuclei in peripheral blood lymphocytes of patients with gynaecological cancer possible implications for the risk of second malignant neoplasms |
| topic | radiotherapy chemotherapy chromosomal damage apoptosis second primary cancers second malignant neoplasms |
| url | https://www.mdpi.com/2073-4409/10/10/2709 |
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