Impact of fractionated cisplatin and radiation treatment on cell growth and accumulation of DNA damage in two normal cell types differing in origin

Impact of fractionated cisplatin and radiation treatment on cell growth and accumulation of DNA damage in two normal cell types differing in origin

Evidence on the impact of chemotherapy on radiotherapy-induced second malignant neoplasms is controversial. We estimated how cisplatin modulates the in vitro response of two normal cell types to fractionated radiation. AHH-1 lymphoblasts and VH10 fibroblasts were irradiated at 1 Gy/fraction 5 and 3...

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Bibliographic Details
Published in:Scientific reports Vol. 13; no. 1; p. 14891
Main Authors: Akuwudike, Pamela, López-Riego, Milagrosa, Dehours, Cloé, Lundholm, Lovisa, Wojcik, Andrzej
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 09-09-2023
Nature Publishing Group
Nature Portfolio
Subjects:
631/67/1059/485
631/67/1059/99
Accumulation
Apoptosis
Carcinogenesis
Cell Biology
Cell death
Cell growth
Cell proliferation
cellbiologi
Chemotherapy
Cisplatin
Deoxyribonucleic acid
DNA
DNA damage
Fibroblasts
fractionation
Humanities and Social Sciences
Lymphoblasts
Molecular Bioscience
molekylär biovetenskap
multidisciplinary
Radiation
Radiation therapy
Science
Science (multidisciplinary)
second malignant neoplasms
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Summary:Evidence on the impact of chemotherapy on radiotherapy-induced second malignant neoplasms is controversial. We estimated how cisplatin modulates the in vitro response of two normal cell types to fractionated radiation. AHH-1 lymphoblasts and VH10 fibroblasts were irradiated at 1 Gy/fraction 5 and 3 times per week during 12 and 19 days, respectively, and simultaneously treated with 0.1, 0.2, 0.4, 0.8, 1.7 and 3.3 µM of cisplatin twice a week. Cell growth during treatment was monitored. Cell growth/cell death and endpoints related to accumulation of DNA damage and, thus, carcinogenesis, were studied up to 21 days post treatment in cells exposed to radiation and the lowest cisplatin doses. Radiation alone significantly reduced cell growth. The impact of cisplatin alone below 3.3 µM was minimal. Except the lowest dose of cisplatin in VH10 cells, cisplatin reduced the inhibitory effect of radiation on cell growth. Delayed cell death was highest in the combination groups while the accumulation of DNA damage did not reveal a clear pattern. In conclusion, fractionated, concomitant exposure to radiation and cisplatin reduces the inhibitory effect of radiation on cell proliferation of normal cells and does not potentiate delayed effects resulting from accumulation of DNA damage.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-39409-7