Biomonitoring 2014; Volume 1: 25–38 Doi: 10.2478/bimo-2014-0003 Received April 3, 2014 accepted May 9, 2014 1 Introduction Testicular cancer represents the most commonly diagnosed cancer in men younger than 35. Its incidence in Europe is on the rise, doubling every two decades [1]. The highest rates of testicular cancer were noted for white Caucasian populations in industrialised countries, mostly in western and northern Europe and Australia/New Zealand [2]. Seminoma is the most common testicular tumour and is believed to arise from the seminiferous epithelium of the mature or maturing testis. Improvements in treatment of testicular cancer have resulted in prolonged survival and high cure rates. For patients with stage I seminoma in particular, regular surveillance, radiotherapy, and/ or carboplatin-based chemotherapy are viable options following an orchidectomy [3]. The prognosis for these patients is good, irrespective of the choice of treatment [4]. Radiotherapy is usually applied in patients with stage I, as adjuvant treatment following a radical inguinal orchidectomy, to minimize the potential relapse in the retroperitoneum and/or ipsilateral pelvis. Furthermore, in patients with stage IIA and IIB, where the regional lymph nodal metastasis is smaller than 5 cm, radiotherapy is given as a definitive therapeutic intervention. In stage IIC, where the regional node metastasis exceeds 5 cm, cisplatin-based combination chemotherapy is commonly used as the primary form of treatment [5]. Here we report a case of a 34-year-old male patient with a stage IB seminoma relapsed in the pelvis two years after surgery and adjuvant radiotherapy. During the second cycle of bleomycin-etoposide-cisplatin (BEP) chemotherapy, he suffered a cerebral infarction. This case is particularly interesting from the clinical point of view because it describes a very rare cisplatin-related Abstract: 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 challenge- test with hydrogen peroxide (H 2 O 2 ) 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 H 2 O 2 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. Keywords: Cisplatin-based chemotherapy, chromosome aberrations, comet assay, irradiation, lymphocyte, micronucleus, testicular cancer Case report Open Access © 2014 Marija Gamulin et al., licensee De Gruyter Open. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License. Marija Gamulin, Ana Pastuhović, Fedor Šantek, Mislav Grgić, Nevenka Kopjar* Biomarkers used to assess radio- and chemotherapy-induced lymphocyte genome instability in a case of cerebral infarction during relapse of a testicular seminoma *Corresponding authors: Nevenka Kopjar: Institute for Medical Re- search and Occupational Health, Mutagenesis Unit, Zagreb, Croatia, Tel. +385 1 46 82 630; Fax +385 1 46 73 303, e-mail: nkopjar@imi.hr Marija Gamulin, Fedor Šantek, Mislav Grgić: Department of Oncology, Clinical Hospital Centre Zagreb, Zagreb, Croatia Ana Pastuhović: School of Medicine, University of Zagreb, Zagreb, Croatia Unauthenticated Download Date | 2/26/20 9:53 AM