Page 49 - ITPS-6-2

INNOSC Theranostics and
Pharmacological Sciences Genotoxicity of (4-fluorophenyl) thiazolidin-4-one

aberrant metaphases (8.63%) out of 301 metaphases,
with 9.95% of aberrations including gaps and 4.9%
excluding gaps. Mitomycin-C induced 90 aberrant % of aberrations excluding gaps 4.96±0.96 26.29±0.96** 29.90±1.87** 29.33±6.76** 40.48±3.03***
metaphases (25.63%) out of 351 metaphases, with 56.41%
of aberrations including gaps, and 40.48% excluding
gaps. During the evaluation, mitomycin-C treated cells
induced a greater number of complex chromosomal
abnormalities like triradial and dicentric chromosomes. % of aberrations including gaps 9.95±1.69 42.22±0.93*** 53.15±1.01*** 58.66±1.20*** 56.41±3.53***
The induction of chromosomal aberrations was found to
be statistically significant at P < 0.001 level compared to
the group treated with DMSO (Table 1). 4-TH compound
at 2.5 µM induced 73 aberrant metaphases (26.76%) out
of 270 metaphases, with 42.22% of aberrations including Total no. of aberrations 30 114 160 176 198
gaps, which were statistically significant compared to
DMSO-treated cells (P < 0.001). Moreover, the percentage
of aberrations excluding gaps was 26.29%, which showed
statistical significance when compared with the vehicle % of aberrant metaphase 8.63±0.85 26.76±1.24*** 33.33±1.85*** 30.00±1.73*** 25.63±0.23***
control (P < 0.01). At an intermediate concentration of
5 µM, 101 aberrant metaphases (33.33%) were observed
out of 301 metaphases, with 53.15% aberrations including Dic 0 16 24 20 25
gaps (P < 0.001), and 29.90% of aberrations excluding
gaps (P < 0.01) compared to DMSO-treated cells. The Qr 0 1 0 0 0
highest concentration of 7.5 µM induced 90 aberrant
metaphases (30%), with 58.66% aberrations including Tr 0 1 1 2 9
gaps, which were statistically significant when compared M 0 4 2 1 7
to the vehicle control (P < 0.001). In addition, the total F 0 2 2 8 4
number of aberrations excluding gaps (29.33%) was Notes: DMSO and mitomycin-C as vehicle and positive controls, respectively. Types of chromosomal aberrations: G: Gaps; B: Breaks; F: Fragment; M: Minute; Tri: Triradial; Qr: Quadra radial;
statistically significant (P < 0.01) when compared to the
vehicle control (Figure 4A-C). Types of aberrations B 1 3 5 8 5 Dic: Dicentric. The level of significance determined in the treated group was compared with the vehicle control using Dunnett’s multiple comparison test. ***P<0.001; **P<0.01;

DNA strand-breaks induced by the toxic agents can Chromosome type of aberrations
manifest as various forms of chromosome aberrations, G 0 5 11 22 11
depending on the phase of the cell cycle. For example, Table 1. Frequency of chromosome aberrations induced by 4‑TH at three different concentrations in CHO‑K1 cells 24‑h post‑treatment
DNA damage occurring during the G1 phase mostly leads
to chromosome aberrations such as chromosome gaps, B 13 17 26 14 46
chromosome breaks, dicentric chromosomes, or ring Chromatidtype of aberrations
chromosomes. On the other hand, when the agent causes
DNA damage during the S-phase of the cell cycle, it primarily G 15 33 48 44 34
results in chromatid aberrations, including chromatid
gaps, breaks, fragments, or minutes [31,36] . Among all the
tested concentrations of 4-TH, the highest concentration No. of aberrant metaphases 26 73 101 90 90
(7.5 µM) induced a higher number of translocations,
ring chromosomes, and other complex chromosomal
aberrations compared to other concentrations. In addition,
this chromosome aberration test confirms that 4-TH at No. of metaphases observed 301 270 301 300 351
all three tested concentrations exhibits highly clastogenic
properties (Table 1).
3.3.2. Mitotic index Dose (µM) 1% 2.5 5 7.5 2.5
To understand the rate of cell division in the presence of
different concentrations of 4-TH, the mitotic index was DMSO (vehicle
analyzed. The cells treated with DMSO exhibited 277 dividing Compound control) Mitomycin-C (positive control) ±: Mean±SEM.
cells (9.12%) out of a total of 6039 cells observed. In contrast, 4-TH

Volume 6 Issue 2 (2023) 6 https://doi.org/10.36922/itps.0618