TY - JOUR
T1 - Characterization of the genotoxic profile of antineoplastic drugs using the cytokinesis-block micronucleus cytome assay
AU - Struys, Ilana
AU - Verscheure, Eline
AU - Lenaerts, Liesbeth
AU - Amant, Frédéric
AU - Godderis, Lode
AU - Ghosh, Manosij
N1 - Funding Information: Funding for this project was provided by ‘ Stichting tegen Kanker ’ (Foundation against Cancer, FAF-F/2018/1264 ), ‘ Kom op tegen Kanker ’ (Stand up against Cancer, Emmanuel van der Schueren Grant) and The Research Foundation - Flanders ( 1SD2322N , 11K6822N ). The funding sources were not involved in study design or preparation of the article. Publisher Copyright: © 2022 Elsevier B.V.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Since antineoplastic agents are frequently used in cancer therapy and able to affect the patient's DNA, it is important to know the genotoxic consequences on non-cancerous tissue. Therefore, we aimed to characterize the genotoxic profile of antineoplastic drugs belonging to different classes, using the cytokinesis-block micronucleus cytome assay in a human monocytic cell line (THP-1). All tested antineoplastic agents resulted in increased micronucleus formation. Exposure to anthracyclines led to an increased number of vacuolated cells and cell death, while for mitotic spindle inhibitors, (different stages of) cell death and an increased nuclear bud formation was observed. Alkylating agents induce a high proportion of vacuolated cells and increased nuclear bud formation. No striking differences of nuclear division index or nucleoplasmic bridge formation were observed between exposed and non-exposed cells. The here presented class-specific aberrations may facilitate interpretation of genotoxic aberrations when evaluating clinical samples from patients treated with these antineoplastic agents.
AB - Since antineoplastic agents are frequently used in cancer therapy and able to affect the patient's DNA, it is important to know the genotoxic consequences on non-cancerous tissue. Therefore, we aimed to characterize the genotoxic profile of antineoplastic drugs belonging to different classes, using the cytokinesis-block micronucleus cytome assay in a human monocytic cell line (THP-1). All tested antineoplastic agents resulted in increased micronucleus formation. Exposure to anthracyclines led to an increased number of vacuolated cells and cell death, while for mitotic spindle inhibitors, (different stages of) cell death and an increased nuclear bud formation was observed. Alkylating agents induce a high proportion of vacuolated cells and increased nuclear bud formation. No striking differences of nuclear division index or nucleoplasmic bridge formation were observed between exposed and non-exposed cells. The here presented class-specific aberrations may facilitate interpretation of genotoxic aberrations when evaluating clinical samples from patients treated with these antineoplastic agents.
KW - Antineoplastic drug
KW - Cytokinesis-block micronucleus cytome assay
KW - Genotoxicity
KW - Micronucleus
UR - http://www.scopus.com/inward/record.url?scp=85143701349&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.etap.2022.104036
DO - https://doi.org/10.1016/j.etap.2022.104036
M3 - Article
C2 - 36503061
SN - 1382-6689
VL - 97
JO - Environmental toxicology and pharmacology
JF - Environmental toxicology and pharmacology
M1 - 104036
ER -