Erythrocyte PIG-A mutant frequencies in cancer patients receiving cisplatin.

Autor: Dobrovolsky VN; Division of Genetic and Molecular Toxicology, National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA), Jefferson, Arkansas, USA., Atiq OT; University of Arkansas for Medical Sciences (UAMS) Winthrop P. Rockefeller Cancer Institute, Little Rock, Arkansas, USA., Heflich RH; Division of Genetic and Molecular Toxicology, National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA), Jefferson, Arkansas, USA., Maisha M; Office of Scientific Coordination, NCTR, FDA, Jefferson, Arkansas, USA., McKinzie PB; Division of Genetic and Molecular Toxicology, National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA), Jefferson, Arkansas, USA., Pearce MG; Division of Genetic and Molecular Toxicology, National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA), Jefferson, Arkansas, USA., Robison TW; Office of New Drugs, OII, DPTII, Center for Drug Evaluation and Research (CDER), US FDA, Silver Spring, Maryland, USA.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2024 Feb; Vol. 13 (3), pp. e6895. Date of Electronic Publication: 2024 Jan 12.
DOI: 10.1002/cam4.6895
Abstrakt: 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.
(© 2024 University of Arkansas for Medical Sciences. Cancer Medicine published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)
Databáze: MEDLINE
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