학술논문
Esencijalni i toksični metali, antioksidacijski enzimi i metalotionein u muškaraca s karcinomom testisa i prostate
Essential and toxic metals, antioxidative enzymes and metallothionein in men with testicular and prostate cancer
Essential and toxic metals, antioxidative enzymes and metallothionein in men with testicular and prostate cancer
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Croatian
Abstract
Neravnoteža između toksičnih i esencijalnih elemenata i sustava antioksidacijske zaštite u organizmu, zajedno s ostalim štetnim čimbenicima iz čovjekovog okoliša i načina života, može dovesti do povećane osjetljivosti i doprinijeti razvoju poremećaja muškog reprodukcijskog sustava kao što su rak testisa i prostate. Cilj ovog istraživanja bio je odrediti povezanost koncentracije esencijalnih i toksičnih metala i polumetala i aktivnosti antioksidacijskih enzima s razinama tumorskih biljega u uzorcima krvi muškaraca s rakom testisa i prostate, uzevši u obzir dob, indeks tjelesne mase, te naviku pušenja i konzumiranja alkohola. Također, određena je koncentracija metalotioneina u serumu ispitanika s rakom testisa, kao i učinak međudjelovanja cinka, selenija i kadmija s platinom na aktivnost superoksid dismutaze i glutation peroksidaze te primarno oštećenje DNA u kontrolnih muškaraca u in vitro uvjetima. U ispitanika s novo dijagnosticiranim rakom testisa izmjerene su značajno niže koncentracije esencijalnih elemenata bakra i selenija i značajno viša koncentracija olova u odnosu na kontrolne ispitanike dok je u skupini ispitanika s novo dijagnosticiranim rakom prostate pronađena značajno viša koncentracija olova i niža koncentracija cinka. U obje skupine ispitanika s malignim oboljenjem uočena je značajno viša aktivnost antioksidacijskih enzima bakar-cink superoksid dismutaze i glutation peroksidaze. U ispitanika s rakom testisa, porastom koncentracije platine nakon primljene kemoterapije, snižene su koncentracije većine mjerenih metala i polumetala, a uočen je porast aktivnosti glutation peroksidaze. U ispitanika s rakom prostate nakon radioterapije, uočen je značajan porast koncentracije bakra i selenija te značajno sniženje koncentracije kadmija i cinka. Dobiveni rezultati pokazali su kako je smanjenje izloženosti toksičnim elementima uz održavanje homeostaze esencijalnih elemenata povezano sa sniženjem razina serumskih tumorskih biljega laktat dehidrogenaze i prostatnog specifičnog antigena. U serumu ispitanika s novo dijagnosticiranim seminomima testisa uočena je viša koncentracija metalotioneina u odnosu na kontrolne ispitanike. Rezultati upućuju na važnost metalotioneina kod germinativnih tumora testisa. U kombinaciji s postojećim biljezima, određivanje metalotioneina moglo bi biti korisno kod dijagnoze raka testisa te u praćenju oboljelih nakon kemoterapije. Na temelju distribucijskog profila platine u serumu ispitanika s germinativnim tumorima testisa možemo zaključiti kako metalotionein ne doprinosi otpornosti na cisplatinu budući da je ~ 95 % slobodne platine vezano za proteine srednje molekulske mase, dok se tek manji dio (~ 3 %) veže za metalotionein. Rezultati ispitivanja međudjelovanja kadmija, platine, selenija i cinka u in vitro uvjetima pokazuju kako istovremeno djelovanje platine i kadmija smanjuje aktivnost bakar-cink superoksid dismutaze (za 16 %) i glutation peroksidaze (za 10 %) te izaziva oštećenje DNA (porast % DNA u repu za 106 % u odnosu na kontrolu), dok je dodatak selenija i cinka rezultirao značajnim povišenjem aktivnosti enzima, odnosno popravkom oštećenja DNA. Ovi rezultati naglašavaju važnost što manje izloženosti kadmiju, pogotovo kod ljudi oboljelih od malignih bolesti koji su, tijekom liječenja, a i kasnije, izloženi spojevima poput cisplatine.
The imbalance between toxic and essential elements and mechanisms of antioxidant defence in the organism, along with other harmful factors from human environment and lifestyle, can lead to increased sensitivity and contribute to the development of the male reproductive system disorders such as testicular and prostate cancer. The aim of this study was to determine the association between the concentration of essential and toxic metals and metalloids and activity of antioxidant enzymes, and levels of tumour markers in blood samples of men with testicular and prostate cancer, taking into account the age, body mass index, smoking habits and alcohol consumption. In addition, we determined the concentration of serum metallothionein in men with testicular cancer, as well as the in vitro interaction of zinc, selenium, cadmium and platinum on the activity of copper-zinc superoxide dismutase and glutathione peroxidase and induction of DNA strand-breaks. In subjects with newly diagnosed testicular cancer we found significantly lower concentrations of essential elements copper and selenium, and higher concentration of lead compared to control subjects, while in subjects with newly diagnosed prostate cancer we found significantly higher concentration of lead and lower concentration of zinc. In both groups of subjects with malignant disease significantly higher activity of antioxidant enzymes copper-zinc superoxide dismutase and glutathione peroxidase was observed. The results show how reducing the exposure to toxic elements while maintaining the homeostasis of essential elements is associated with decrease in serum levels of tumour markers lactate dehydrogenase and prostate specific antigen. Increased concentration of platinum in patients with testicular cancer after chemotherapy reduced the bioavailability of most metals and metalloids and activated the antioxidant defence mechanisms. In patients with prostate cancer, concentration of copper and selenium significantly increased after radiotherapy while there was a decrease in concentration of cadmium and zinc. In subjects with newly diagnosed testicular seminoma we found significantly higher concentration of metallothionein compared to control. In combination with the existing markers, the determination of serum metallothionein levels could be useful in diagnosis of testicular cancer and in monitoring patients after chemotherapy. Based on the distribution profile of platinum in the serum of patients with testicular cancer, we can conclude that metallothionein does not contribute to cisplatin resistance since ~ 95% of serum platinum binds to medium molecular mass proteins while only ~ 3% is bound to metallothionein. The results of in vitro experiment regarding interactions of cadmium, platinum, selenium and zinc in blood show that simultaneous addition of cadmium and platinum reduces the activity of copper-zinc superoxide dismutase (by 16%) and glutathione peroxidase (by 10%) and induces DNA damage. However, addition of selenium and zinc recovered enzyme activity and repaired the DNA damage. These results emphasize the importance of the less exposure to cadmium, especially for people with malignant disease who are, during treatment and later, exposed to compounds such as cisplatin.
The imbalance between toxic and essential elements and mechanisms of antioxidant defence in the organism, along with other harmful factors from human environment and lifestyle, can lead to increased sensitivity and contribute to the development of the male reproductive system disorders such as testicular and prostate cancer. The aim of this study was to determine the association between the concentration of essential and toxic metals and metalloids and activity of antioxidant enzymes, and levels of tumour markers in blood samples of men with testicular and prostate cancer, taking into account the age, body mass index, smoking habits and alcohol consumption. In addition, we determined the concentration of serum metallothionein in men with testicular cancer, as well as the in vitro interaction of zinc, selenium, cadmium and platinum on the activity of copper-zinc superoxide dismutase and glutathione peroxidase and induction of DNA strand-breaks. In subjects with newly diagnosed testicular cancer we found significantly lower concentrations of essential elements copper and selenium, and higher concentration of lead compared to control subjects, while in subjects with newly diagnosed prostate cancer we found significantly higher concentration of lead and lower concentration of zinc. In both groups of subjects with malignant disease significantly higher activity of antioxidant enzymes copper-zinc superoxide dismutase and glutathione peroxidase was observed. The results show how reducing the exposure to toxic elements while maintaining the homeostasis of essential elements is associated with decrease in serum levels of tumour markers lactate dehydrogenase and prostate specific antigen. Increased concentration of platinum in patients with testicular cancer after chemotherapy reduced the bioavailability of most metals and metalloids and activated the antioxidant defence mechanisms. In patients with prostate cancer, concentration of copper and selenium significantly increased after radiotherapy while there was a decrease in concentration of cadmium and zinc. In subjects with newly diagnosed testicular seminoma we found significantly higher concentration of metallothionein compared to control. In combination with the existing markers, the determination of serum metallothionein levels could be useful in diagnosis of testicular cancer and in monitoring patients after chemotherapy. Based on the distribution profile of platinum in the serum of patients with testicular cancer, we can conclude that metallothionein does not contribute to cisplatin resistance since ~ 95% of serum platinum binds to medium molecular mass proteins while only ~ 3% is bound to metallothionein. The results of in vitro experiment regarding interactions of cadmium, platinum, selenium and zinc in blood show that simultaneous addition of cadmium and platinum reduces the activity of copper-zinc superoxide dismutase (by 16%) and glutathione peroxidase (by 10%) and induces DNA damage. However, addition of selenium and zinc recovered enzyme activity and repaired the DNA damage. These results emphasize the importance of the less exposure to cadmium, especially for people with malignant disease who are, during treatment and later, exposed to compounds such as cisplatin.