scholarly journals Influence of GSTT1 and GSTM1 null genotypes on differentiated thyroid cancer risk and baseline and radioiodine induced cytogenetic damage in peripheral blood lymphocytes of patients

Genetika ◽  
2017 ◽  
Vol 49 (2) ◽  
pp. 599-611
Author(s):  
Olivera Milosevic-Djordjevic ◽  
Darko Grujicic ◽  
Marina Radovic-Jakovljevic ◽  
Dragoslav Marinkovic ◽  
Sladjana Dimitrijevic ◽  
...  

As it is known that genetic polymorphisms of glutathione S-transferases (GST) have been associated with a variety of human diseases including cancer, we have analyzed the impact of GSTT1 and GSTM1 null genotypes on the risk of development of differentiated thyroid cancer (DTC) and cytogenetic changes in peripheral blood lymphocytes of DTC patients before and after radioiodine therapy. The polymorphism of GSTT1 and GSTM1 genes were genotyped using multiplex polymerase chain reaction (PCR) and cytokinesis - block micronucleus (MN) assay to assess cytogenetic changes. GSTT1 and GSTM1 null were predominantly found in patients, but statistical significance was observed only for GSTT1 null. The null genotypes increased risk of development of DTC; GSTT1 null a 4.5 times (p < 0.05), GSTM1 null about 3 times but on the border of statistical significance (p = 0.057), while combination of dual null genotypes almost 7 times (p < 0.05) increased risk. No significant effects of the null genotypes as well as their interactions with potential modifiers of MN (diagnose, age, gender and smoking habits) were observed on both baseline and radioiodine-induced values of MN and cytokinesis block proliferation index (CBPI) in DTC patients. Results suggest that both GSTT1 and GSTM1 null genotypes increased risk for DTC but to a greater extent GSTT1 null. Null genotypes of GSTT1 and GSTM1 did not have potential to influence baseline and radioiodine-induced values of MN and CBPI, so that absence of T1 and M1 isoenzymes did not cause increased mutagen sensitivity of PBLs of DTC patients.

Neoplasma ◽  
2013 ◽  
Vol 60 (05) ◽  
pp. 568-575 ◽  
Author(s):  
O. Vrndic ◽  
O. Milosevic-Djordjevic ◽  
P. Djurdjevic ◽  
D. Jovanovic ◽  
L. Mijatovic ◽  
...  

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 658 ◽  
Author(s):  
Gabriela Gajek ◽  
Beata Marciniak ◽  
Jarosław Lewkowski ◽  
Renata Kontek

The incidence of gastrointestinal cancers is increasing every year. Irinotecan (CPT-11), a drug used in the treatment of colorectal cancer and gastric cancer, is metabolized by carboxylesterases to an active metabolite, SN-38, which is more cytotoxic. CAPE (caffeic acid phenethyl ester) is an active component of propolis, which has a high antibacterial, antiviral, and antineoplastic potential. This study analyses the impact of CAPE on the cytotoxic (MTT assay), genotoxic (comet assay) and proapoptotic (caspase-3/7 activity) potential of irinotecan and its metabolite SN-38 in cultures of gastrointestinal neoplastic cells (HCT116, HT29, AGS). Cytotoxicity and genotoxicity activities of these compounds were carried out in comparison with human peripheral blood lymphocytes (PBLs) in vitro. The antioxidant potential of CAPE was investigated in relation H2O2-induced oxidative stress in the both neoplastic cells and PBLs. CAPE expressed cytotoxic, genotoxic, and pro-apoptotic activity against AGS, HCT116, and HT29 tumor cells. CAPE, in the presence of different concentrations of irinotecan or SN38, decreased the cytotoxicity, genotoxicity, and pro-apoptotic activity in these cell lines, but it has no such action on normal human peripheral blood lymphocytes.


1986 ◽  
Vol 70 (s13) ◽  
pp. 29P-29P
Author(s):  
T. Brown ◽  
A.A. Dawson ◽  
J.L. Watt ◽  
R.L. Himsworth

2015 ◽  
Vol 57 (2) ◽  
pp. 173-179 ◽  
Author(s):  
U. Eberlein ◽  
H. Scherthan ◽  
C. Bluemel ◽  
M. Peper ◽  
C. Lapa ◽  
...  

2018 ◽  
Vol 62 (3) ◽  
pp. 41-47
Author(s):  
R. Michalková ◽  
K. Šiviková ◽  
M. Galdíková

Abstract The potential genotoxic/cytotoxic effect of epoxiconazole was evaluated by means of sister chromatid exchanges (SCE) following the 24 and 48 h in vitro exposure of human peripheral blood lymphocytes to epoxiconazole at concentrations of: 5, 10, 25, 50 and 100 μg. ml–1. Dimethyl sulphoxide (DMSO), used as an epoxiconazole solvent, was used as a negative control and mitomycine (MMC) as a positive control. After the 24-hour exposure, we failed to observe a significant increase in SCE frequencies in comparison with the negative control, however, the concentrations of 10—100 μg.ml–1 caused a significant decrease in the proliferation index (PI; P < 0.001). Also, the 48-hour exposure produced no significant alterations in the SCE frequencies in comparison with the control. At epoxiconazole concentrations ranging from 10 to 50 μg.ml–1 we recorded a moderate to strong, dose-dependent inhibition of PI (P < 0.05; P < 0.01; P < 0.001), while at the highest dose (100 μg.ml–1) the reduction in PI compared to the control was less pronounced (P < 0.05). The reduction in PI at the concentration range of 10—100 μg.ml–1 depended on the number of cells in the M1, M2 and M3 phases of the cell cycle per total number of 100 evaluated metaphases. Our results indicated a significant cytotoxic or cytostatic effect on human peripheral blood lymphocytes.


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