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Biomarkers used to assess radio- and chemotherapy-induced lymphocyte genome instability in a case of cerebral infarction during relapse of a testicular seminoma

100%

Gamulin M., Pastuhović A., Šantek F., Grgić M., Kopjar N.

Biomonitoring

2014

vol. 1

issue 1

We report a case of a testicular seminoma patient with relapse who was irradiated after acute cerebral infarction induced by cisplatin-based chemotherapy. Lymphocytic genome instability was studied using an alkaline comet assay, analysis of structural chromosome aberrations, and cytokinesis-block micronucleus assay in blood samples collected before and after PET CT scanning that preceded radiotherapy, as well as before the administration of the first and after the administration of the last fraction of 3D conformal radiation. A challengetest with hydrogen peroxide (H2O2) was performed on isolated peripheral blood lymphocytes in order to establish to what extent earlier therapies had modified the response of the patient’s DNA to external stimuli with a genotoxic chemical. Levels of primary DNA damage in lymphocytes increased after diagnostic exposure, lowered prior to administration of a conformal 3D radiotherapy, and were the highest at the end of radiotherapy. Ex vivo exposure to H2O2 caused additional lymphocyte DNA damage, which gradually increased 15 and 30 minutes after treatment. Diagnostic and therapeutic exposure to radiation caused measurable cytogenetic damage that was subjected to extensive repair. All of the obtained results point to increased genomic instability in the patient which should be taken into account in his future medical surveillance.

Evaluation of HI-6 oxime: potential use in protection of human acetylcholinesterase inhibited by antineoplastic drug irinotecan and its cyto/genotoxicity in vitro

84%

Radić B., Vrdoljak A. L., Želježić D., Fuchs N., Berend S., Kopjar N.

Acta Biochimica Polonica

2007

vol. 54

issue 3

583-593

The function of acetylcholinesterase (AChE) is the rapid hydrolysis of the neurotransmitter acetylcholine (ACh), which is involved in the numerous cholinergic pathways in both the central and the peripheral nervous system. Therefore, AChE measurement is of high value for therapy management, especially during the course of intoxication with different chemicals or drugs that inhibit the enzyme. Pyridinium or bispyridinium aldoximes (oximes) are able to recover the activity of the inhibited enzyme. Since their adverse effects are not well elucidated, in this study the efficiency of HI-6 oxime in protection and/or reactivation of human erythrocyte AChE inhibited by the antineoplastic drug irinotecan as well as its cyto/genotoxicity in vitro were investigated. HI-6 was effective in protection of AChE and increased its activity up to 30%; the residual activity after irinotecan inhibition was 7%. Also, it reactivated the enzyme previously inhibited by 50% irinotecan (4.6 µg/ml) applied at ¼ of the IC50 value. The tested concentrations of HI-6 exhibited acceptable genotoxicity towards white blood cells, as estimated by the alkaline comet assay, DNA diffusion assay and cytogenetic endpoints (structural chromosome aberrations and cytokinesis-block micronucleus assay). The results obtained warrant the further investigation of HI-6 in vivo, as well as its development for possible application in chemotherapy.

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1 Acta Biochimica Polonica

1 Biomonitoring

1 2014

1 2007

2 Kopjar N.

1 Berend S.

1 Fuchs N.

1 Gamulin M.

1 Grgić M.

1 Pastuhović A.

1 Radić B.

1 Vrdoljak A. L.

1 Šantek F.

1 Želježić D.

Search results

Biomarkers used to assess radio- and chemotherapy-induced lymphocyte genome instability in a case of cerebral infarction during relapse of a testicular seminoma

Evaluation of HI-6 oxime: potential use in protection of human acetylcholinesterase inhibited by antineoplastic drug irinotecan and its cyto/genotoxicity in vitro