Evaluation of the genotoxic effects of the boron neutron capture reaction in human melanoma cells using the cytokinesis block micronucleus assay

Abstract

The present work reports on the genotoxicity of the boron neutron capture (BNC) reaction in human metastatic melanoma cells (A2058) assessed by the cytokinesis block micronucleus assay (CBMN) using p-borono-L-phenylalanine (BPA) as the boron delivery agent. Different concentrations of BPA (0.48, 1.2 and 2.4 mM) and different fluences of thermal neutrons were studied. Substantial genotoxic potential of alpha and lithium particles generated inside or near the malignant cell by the BNC reaction was observed in a dose-response manner as measured by the frequency of micronucleated binucleated melanoma cells and by the number of micronuclei (MN) per binucleated cell. The distribution of the number of MN per micronucleated binucleated cell was also studied. The BNC reaction clearly modifies this distribution, increasing the frequency of micronucleated cells with 2 and, especially, > or =3 MN and conversely decreasing the frequency of micronucleated cells with 1 MN. A decrease in cell proliferation was also observed which correlated with MN formation. A discrete genotoxic and anti-proliferative contribution from both thermal neutron irradiation and BPA was observed and should be considered secondary. Additionally, V79 Chinese hamster cells (chromosomal aberrations assay) and human lymphocytes (CBMN assay) incubated with different concentrations of BPA alone did not show any evidence of genotoxicity. The presented results reinforce the usefulness of the CBMN assay as an alternative method for assessment of the deleterious effects induced by high LET radiation produced by the BNC reaction in human melanoma cells.

First Evaluation of the Biologic Effectiveness Factors of Boron Neutron Capture Therapy (BNCT) in a Human Colon Carcinoma Cell Line

“…On the other hand, we can exclude that BPA and BOPP have genotoxic effects per se in the administered doses. These results agree with studies published elsewhere that have shown no cytotoxic or genotoxic effects for these boron compounds (18,19).…”

Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

“…High LET radiations, such as α particles, induce more extensive delays in the S or G2 phase compared with low LET radiations [25], due to the different radiobiological effects of high LET particle beams with respect to impacts on cell cycle control [26]. Our results showed that cell cycle was arrested at the G2/M checkpoint in SHG-44 and SU2 cells after BNCT.…”

Three new labdanes isolated from Eragrostis viscosa

“…Micronuclei were identified under a light microscope using a magnification of 1250 × according to the criteria proposed by Caria et al 15 It was evaluated the MN/BN value, which represents the average number of micronuclei per binucleated cell, and the percentage MNBN, which represents the fraction of cytokinesis-blocked (binucleated) cells with micronuclei, regardless of the number of micronuclei per BN cell. 16 The decrease in cell proliferation was also measured in these assays by determining the frequency of binucleate cells (BN, %). For this index, the number of nuclei in 1000 cells with well-preserved cytoplasms was determined at a magnification of 500×.…”