The Oxidative Stress Parameters as Useful Tools in Evaluating the DNA Damage and Changes in the Complete Blood Count in Hospital Workers Exposed to Low Doses of Antineoplastic Drugs and Ionizing Radiation.

Hospital workers at the Oncology Department are occupationally exposed to antineoplastic drugs (ANTNP) or low doses of ionizing radiation (Irrad). Therefore, the aim of this study was to evaluate the level of DNA damage, the oxidative stress parameters and complete blood count (CBC) of hospital workers in order to analyze the negative health effects of ANTNP and low dose Irrad. The frequency of micronuclei (MN) and proliferation index (PI) were analyzed by cytokinesis-block test. The oxidative stress biomarkers evaluated were the level of lipid peroxidation in plasma and catalase activity (CAT) in erythrocytes. A group of 86 hospital workers (35 exposed to ANTPN and 51 to Irrad) had increased MN frequency, CAT activity and level of lipid peroxidation compared to the control group, which consisted of 24 volunteers. The hemoglobin level was lower in the ANTNP group compared to thecontrol group, while a significant difference in RBC was recorded between thecontrol and Irrad groups, and in platelet count betweentheIrrad and ANTNP group. The results showed increased DNA damage, oxidative stress parameters, as well as impairment on complete blood count in hospital workers occupationally exposed to antineoplastic drugs and low-dose ionizing radiation. As this research has shown the importance of oxidative stress, we suggest that in addition to routine methods in periodic medical evaluation, the possibility of applying oxidative stress parameters is considered. Moreover, hospital workers exposed to ANTNP and Irrad in the workplace should undergo not only a more complete health prevention procedure but also have a more appropriate health promotion.

Accidental Use of Milk With an Increased Concentration of Aflatoxins Causes Significant DNA Damage in Hospital Workers Exposed to Ionizing Radiation.

The occupational exposure to ionizing radiation (Irad) or associated with mycotoxin-contaminated food may lead to genome damage and contribute to health risk. DNA damage in 80 blood samples of hospital workers occupationally exposed to low-doses of Irad was compared with 80 healthy controls. Among them, 40 participants accidentally consumed milk with increased concentration of Aflatoxin. All participants underwent the testing for micronuclei from blood, and 40 of them 8-OHdG from urine. The frequency of micronuclei (MN) was analyzed by cytokinesis-block peripheral blood lymphocytes and the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) by ELISA. The Irad led to increased frequency of MN (p < 0.05) and 8-OHdG level at exposed hospital workers. The consumption of milk with increased concentration of aflatoxin probably raised MN frequency and 8-OHdG value. Higher consumption of aflatoxin-contaminated milk (≥2 L/monthly) caused significantly increased MN frequency and 8-OHdG value in comparison to lower milk intake (≤0.5 L/monthly). Also, confounding factors, such as age, gender, and smoking status of all participants were included in the study. The obtained results revealed an increased incidence of MN and 8-OHdG level among hospital workers exposed to low-doses of IRad and milk with increased aflatoxin concentration.

A Review of the Therapeutic Antitumor Potential of Cannabinoids.

OBJECTIVES: The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment. METHODS: A literature survey of medical and scientific databases was conducted with a focus on the biological and medical potential of cannabinoids in cancer treatment. RESULTS: Cannabis sativa is a plant rich in more than 100 types of cannabinoids. Besides exogenous plant cannabinoids, mammalian endocannabinoids and synthetic cannabinoid analogues have been identified. Cannabinoid receptors type 1 (CB1) and type 2 (CB2) have been isolated and characterized from mammalian cells. Through cannabinoid receptor and non-receptor signaling pathways, cannabinoids show specific cytotoxicity against tumor cells, while protecting healthy tissue from apoptosis. The dual antiproliferative and proapoptotic effects of cannabinoids and associated signaling pathways have been investigated on a large panel of cancer cell lines. Cannabinoids also display potent anticancer activity against tumor xenografts, including tumors that express high resistance to standard chemotherapeutics. Few studies have investigated the possible synergistic effects of cannabinoids with standard oncology therapies, and are based on the preclinically confirmed concept of "cannabinoid sensitizers." Also, clinical trials aimed to confirm the antineoplastic activity of cannabinoids have only been evaluated on a small number of subjects, with no consensus conclusions regarding their effectiveness. CONCLUSIONS: A large number of cannabinoid compounds have been discovered, developed, and used to study the effects of cannabinoids on cancers in model systems. However, few clinical trials have been conducted on the use of cannabinoids in the treatment of cancers in humans. Further studies require extensive monitoring of the effects of cannabinoids alone or in combination with standard anticancer strategies. With such knowledge, cannabinoids could become a therapy of choice in contemporary oncology.

Dose-dependent survival of K562 cells subjected to irradiation, time course of endogenous enzyme activity and protective effect of applied superoxide dismutase.

PURPOSE: Irradiation-generated reactive species are proven to affect the cell survival and antioxidant enzyme levels. Radioresistance is a phenomenon which includes many cell mechanisms and signaling pathways. Superoxide dismutase (SOD) acts in and outside of cells after irradiation. The aim of this study was to determine LD50 (lethal dose for 50% of K562 cells), to monitor the effect of a chosen dose and exogenously applied superoxide dismutase (ExSOD) on the cell number and the activity of SOD, glutathione peroxidase (GSH-Px) and catalase (CAT). METHODS: The survival of irradiated (20-32.5 Gy) K562 cells was determined using the trypan-blue exclusion. Besides irradiated and non-irradiated cells (controls), another two groups of cells were treated with SOD (10-6 M) which then served as SOD-treated controls or were irradiated (30 Gy) one hour later. The number of cells and the activity of SOD, GSH-Px and CAT (using kinetic methods) were monitored after 1, 24, 48, 72 and 96 hrs in unirradiated, irradiated, SOD-treated and SOD-treated/irradiated experimental groups. RESULTS: K562 cells showed dose-dependent survival in the chosen range of doses. A dose of 30 Gy induced 50% cell mortality and increased the activity of all three investigated enzymes after 24 hrs. Pretreatment with SOD preserved the survival of irradiated cells and increased SOD, GSH-Px and CAT activity. ExSOD induced an increase of the activity of all examined enzymes. CONCLUSION: A balanced enhancement in endogenous antioxidative activity may be the cause of the increased radioresistance of K562 SOD-pretreated cells.

Effects of orally administered antioxidants on micronuclei and sister chromatid exchange frequency in workers professionally exposed to antineoplastic agents.

The widespread use of antineoplastic drugs in cancer treatment increased concern about possible hazard to workers involved in the preparation and administration of these drugs. In the present study, the effects of commercial antioxidative drug Oligogal Se on genome protection were analyzed in 15 nurses handling the antineoplastic drugs at the Oncology Department in comparison to twenty healthy volunteers. The nurses took antioxidant mixture Oligogal Se, consisting of vitamins C, E, A and selenium, one capsule per day, over a period of 6 months. Genome damage was measured in peripheral blood lymphocytes by usage of sister chromatid exchange test and the cytokinesis-block micronuclei test. The frequency of sister chromatid exchange (SCE) and micronuclei (MN) in the exposed group was significantly higher when compared to the control group (SCE, p<0.05; MN, p<0.01 respectively). After antioxidant supplementation, the frequency of sister chromatid exchange and micronuclei decreased (p<0.05) when compared with the values from the beginning of the study, but were still above the values of the control group. The effects of confounding factors such as cigarette smoking and cytostatics exposure time were also evaluated. The data indicated that Oligogal Se contributed to the decreasing of genome damages in workers handling the cytostatics.

Effects of fullerenol C60(OH)24 on the frequency of micronuclei and chromosome aberrations in CHO-K1 cells.

Poly-hydroxylated C(60) fullerenols (C(60)(OH)(n)) have attracted much attention in biomedical research, due to a variety of biological activities. However, the studies investigating the genotoxic effects of fullerenols are still insufficient. The aim of the present study was to analyze the genotoxic and antigenotoxic potential of fullerenol C(60)(OH)(24). The investigation was carried out with mitomycin C (MMC)-treated and control Chinese hamster ovary cells (CHO-K1), using the chromosome aberration (CA) assay and the cytokinesis-block micronucleus (CBMN) test. Cells were treated with fullerenol nanoparticles, which are well known for their antioxidative properties and cytoprotective effects, both in vivo and in vitro. Our study showed the absence of genotoxicity of fullerenol in a wide range of concentrations (11-221 microM). Fullerenol mediated the decrease in the frequency of micronuclei (MN) and chromosome aberrations compared with the controls at all endpoints examined. A dose-dependent decrease of MN frequency was found 24h after treatment with fullerenol, in contrast to the outcome of the CA assay. Cell proliferation was equally influenced by fullerenol. The majority of aberrations were of the chromosome-type. Our results show that fullerenol does not induce genotoxic effects, and that it protects both non-damaged and MMC-damaged CHO-K1 cells.

Fullerenol C60(OH)24 effects on antioxidative enzymes activity in irradiated human erythroleukemia cell line.

Radiotherapy-induced toxicity is a major dose-limiting factor in anti-cancer treatment. Ionizing radiation leads to the formation of reactive oxygen and nitrogen species (ROS/RNS) that are associated with radiation-induced cell death. Investigations of biological effects of fullerenol have provided evidence for its ROS/RNS scavenger properties in vitro and radioprotective efficiency in vivo. Therefore we were interested to evaluate its radioprotective properties in vitro in the human erythroleukemia cell line. Pre-treatment of irradiated cells by fullerenol exerted statistically significant effects on cell numbers and the response of antioxidative enzymes to X-ray irradiation-induced oxidative stress in cells. Our study provides evidence that the pre-treatment with fullerenol enhanced the enzymatic activity of superoxide dismutase and glutathione peroxidase in irradiated K562 cells.