Aleksandra Fucic

Institute for Medical Research and Occupational Health

Aim To compare interleukin-2 levels (IL-2) and IL-2 gene site 1 methylation levels between preterm newborns (PN) and full-term newborns (FN) and investigate their association with the environmental exposure of their mothers during pregnancy. Methods IL-2 and IL-2 gene site 1 methylation levels were assessed in 50 PN and 56 FN. Newborns’ mothers fi...

Within the EU human biomonitoring initiative (HBM4EU), a targeted, multi-national study on occupational exposure to hexavalent chromium (Cr(VI)) was performed. Cr(VI) is currently regulated in EU under REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) and under occupational safety and health (OSH) legislation. It has rece...

A study was conducted within the European Human Biomonitoring Initiative (HBM4EU) to characterize occupational exposure to Cr(VI). Herein we present the results of biomarkers of genotoxicity and oxidative stress, including micronucleus analysis in lymphocytes and reticulocytes, the comet assay in whole blood, and malondialdehyde and 8-oxo-2′-deoxyg...

Male infertility, a condition that has during the last decade raised significant concern, is a diagnostically demanding and socially sensitive topic. The number of unsolved issues on infertility etiology, especially potential environmental causes, in couples demonstrates the need for further investigations into infertility biomarkers. Semen paramet...

Background: Currently coal mining employs over 7 million miners globally. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons and radioactive radon, significantly increasing the risk of lung cancer (LC). The susceptibility for LC is modified by genetic variations in xenobiotic det...

Despite the great efforts of basic and clinical research on lung cancer (LC), the prevention and treatment of this type of cancer show still far from satisfactory indicators. The complex mechanisms of the LC biology are already recognized, but there is a significant gap in the knowledge about the interaction of key biomarkers in the etiology and pr...

Background: Male infertility is increasingly becoming a health and demographic problem. While it may originate from congenital or acquired diseases, it can also result from environmental exposure. Hence, the complexity of involved molecular mechanisms often requires a multiparametric approach. This study aimed to associate semen parameters with sp...

Estradiol (E), testosterone (T), and their ratio are crucial axis in life. Especially during intrauterine growth, they orchestrate the complex development of organs and their interaction, which have lifelong impact on health and an organism’s capacity to respond to environmental stressors. The aim of this study was to compare for the first time E,...

A marked reduction in fertility and an increase in adverse reproductive outcomes during the last few decades have been associated with occupational and environmental chemical exposures. Exposure to different types of pesticides may increase the risks of chronic diseases, such as diabetes, cancer, and neurodegenerative disease, but also of reduced f...

The upsurge in male infertility over the last two decades, possibly due to environmental exposure, has raised significant interest, particularly boosted by reports from fertility clinics, which showed that chronic diseases and hereditary or other medical conditions might only partially explain current incidence of male infertility. Both environment...

Objectives: Oral squamous cell carcinoma (OSCC) is the most common oral malignancy with low survival as it is very often diagnosed at an advanced stage, which is why the accurate profiling of the tumor is essential. The aim of this study was to, for the first time, compare in OSCC the frequency of AR, VEGF, MMP9, HiF1beta and Ki67 between the non-...

Recent findings indicate that the microbiome may have significant impact on the development of lung cancer by its effects on inflammation, dysbiosis or genome damage. The aim of this study was to compare the sputum microbiome of lung cancer (LC) patients with the chromosomal aberration (CA) and micronuclei (MN) frequency in peripheral blood lymphoc...

Introduction Phthalates, a group of ubiquitous industrial chemicals, have been widely used in occupational settings, mainly as plasticizers in a variety of applications. Occupational exposure to different phthalates has been studied in several occupational settings using human biomonitoring (HBM). Aim To provide a comprehensive review of the avail...

Background: The aim of this study was to compare for the first time IL-6 (Interleukin 6), testosterone (T) and estradiol (E) levels, their ratio (E/T), micronucleus (MN), and nuclear bridge (NB) frequency between newborns with regard to their mother’s residency and diet. Our results should enable an assessment of the possible environmental endocrin...

New molecular cytogenetic biomarkers may significantly contribute to biodosimetry, whose application is still globally diverse and not fully standardized. In 2011, a new term, chromothripsis, was introduced raising great interest among researchers and soon motivating further investigations of the phenomenon. Chromothripsis is described as a single...

Background/Aim: Oral squamous cell carcinoma (OSCC) is a cancer with poor prognosis due to therapy resistance, locoregional recurrences, and distant metastases. There is on increased interest in profiling the androgen receptor (AR) in cancer biology. The aim of this study was to compare AR and Ki-67 levels in the neoplastic epithelium and stroma be...

Purpose Lung cancer (LC) is the leading cause of death in the world. Introduction of early biomarkers of LC risk and efficacy of therapy are priorities in preventive programs and follow-up of patients during and after therapy. Genome instability expressed via structural and numerical genome damage similar to other cancer types is also a known mecha...

Objectives: The high incidence of head and neck cancer (HNC), significantly associated with living environment and behaviour, can be prevented more efficiently. The aim of this study was to evaluate the environmental and behavioural risk factors for HNC. Methods: Using a detailed questionnaire on social status, education, living and occupational...

Objectives: The high incidence of head and neck cancer (HNC), significantly associated with living environment and behaviour, can be prevented more efficiently. The aim of this study was to evaluate the environmental and behavioural risk factors for HNC. Methods: Using a detailed questionnaire on social status, education, living and occupational en...

Ehlers-Danlos syndrome (EDS) is a heritable connective tissue disorder characterized by skin hyperextensibility, abnormal wound healing, and joint hypermobility with prevalence 1:20 000. Its incidence is probably underestimated due to unknown number of subjects having mild symptoms who may have never been diagnosed through entire life time. Classic...

Large investments by pharmaceutical companies in the development of new antineoplastic drugs have not been resulting in adequate advances of new therapies. Despite the introduction of new methods, technologies, translational medicine and bioinformatics, the usage of collected knowledge is unsatisfactory. In this paper, using examples of pancreatic...

Endocrine disruptors (EDs) belong to large and diverse groups of agents that may cause multiple biological effects associated with, for example, hormone imbalance and infertility, chronic diseases such as diabetes, genome damage and cancer. The health risks related with the exposure to EDs are typically underestimated, less well characterized, and...

The living environment is a multilevel physical and chemical xenobiotic complex with potentially mutagenic effects and health risks. In addition to inorganic exposures, all terrestrial and aquatic living forms interact with microbiota as selectively established communities of bacteria, viruses and fungi. Along these lines, the human organism should...

Recent publications have highlighted a greater utility of routine blood tests in patients with various cancers than previously assumed. It appears that the neutrophil-to-lymphocyte ratio (NLR) may be a good predictive biomarker for overall survival (OS) and disease-free survival (DFS). Preoperative and postoperative NLR data for patients with head...

Lung cancer is one of the most common forms of cancer. The aim of this study was to validate chromosome aberrations in peripheral blood lymphocytes of lung cancer patients living in a region with high air pollution and increased background radon levels as a biomarker of cancer risk. A total of 417 lung cancer patients and 468 control participants w...

The worldwide annual incidence of oral squamous cell carcinoma (OSCC) is over 300,000 cases with a mortality rate of 48%. This cancer type accounts for 90% of all oral cancers, with the highest incidence in men over 50 years of age. A significantly increased risk of developing OSCC exists among smokers and people who consume alcohol daily. OSCC is...

Background: The RAS association domain family protein 1a (RASSF1A) is a prominent tumor suppressor gene showing altered promoter methylation in testicular germ cell tumors (TGCT). RASSF1A promoter hypermethylation might represent an early event in TGCT tumorigenesis. We investigated whether the RASSF1A promoter methylation in peripheral blood of T...

Biological responses to carcinogens from environmental exposure during adulthood are modulated over years or decades. Conversely, during transplacental exposure, the effects on the human foetus change within weeks, intertwining with developmental mechanisms: even short periods of transplacental exposure may be imprinted in the organism for a lifeti...

Diabetes is associated with certain environmental exposures, heritable factors, and metabolic conditions of intrauterine development due to diabetes in the mother. We evaluated genomic damage, cell-free DNA, N-glycosylation of umbilical cord plasma proteins (PG), and nuclear division index (NDI) as possible prognostic biomarkers of health risk in t...

Background: Gender difference in survival of patients with gastric cancer is not well investigated. The aim of this study was to analyze the gender-related distribution of estrogen receptor alpha (ERα) and androgen receptor (AR) in the epithelium and stroma of intestinal-type gastric cancer. Materials and methods: Immunohistochemical analysis wa...

Epilepsy is the most common neurological complication in pregnancy. Women with epilepsy have a higher risk of complications in pregnancy. In Croatia, women with epilepsy are treated by neurologists at tertiary centers according to the place of residence. We prospectively followed-up pregnancies in women with epilepsy and healthy controls, and analy...

As children are more susceptible to ionizing radiation than adults, each nuclear accident demands special attention and care of this vulnerable population. The Chernobyl nuclear disaster occurred in a region populated with a large number of children, but despite all efforts and expertise of nuclear specialists, it was not possible to avoid casualti...

The mechanisms that lead to sex and age differences in biological responses to exposure to ionising radiation and related health risks have still not been investigated to a satisfactory extent. The significance of sex hormones in the aetiology of radiogenic cancer types requires a better understanding of the mechanisms involved, especially during o...

Background/aim: Biomonitoring is currently applied in the estimation of health risks after overexposure to ionizing radiation (IR). The aim of this study was to compare the association of dicentric chromosomes and acentric fragments (AF) with cancer risk in subjects exposed to IR, as well as in control subjects. Materials and methods: The study...

Cells with specific multiple chromosome aberrations, defined as rogue cells (RC) have been described in different populations, predominantly those exposed to radiation. The frequency, etiology and related health risks have still not been elucidated due to their low frequency of occurrences and rarely performed studies. This study reports RC frequen...

In 2013–2015, a consortium of European scientists – NEWDANUBE – was established to prepare a birth cohort in the Danube region, including most of the countries with the highest air pollution in Europe, the area being one-fifth of the European Union’s (EU’s) territory, including 14 countries (nine EU member states), over 100 million inhabitants, wit...

Susceptibility to environmental stressors, same as cancer incidence is both age and gender related. Understanding the complexity of responses to living environment has been impaireddue to research based on reductionisms and lack of methods, models and sophisticated softwares which enable analysis of complex pathways which may be disturbed by xenobo...

Data on the possible genotoxic effects of testosterone are limited: in particular, the potential clastogenic and/or aneugenic effects have not yet been properly investigated. An in vitro micronucleus (MN) assay was performed on L929 cells exposed to testosterone at doses of 10, 15, 20, 30, and 40μg/mL. Significantly increased MN frequencies were de...

a b s t r a c t Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current s...

Vanek's tumor is an inflammatory fibroid polyp (IFP) of very low incidence, which originates in the submucosa of the stomach, duodenum, jejunum and ileum. The etiology of this tumor is still unknown. Histologically, IFP is characterized by submucosal spindle cell proliferation in fibromyxoid stroma with inflammatory infiltrate. The aim of the prese...

Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male...

Data on genome damage, lipid peroxidation, and levels of glutathione peroxidase (GPX) in newborns after transplacental exposure to xenobiotics are rare and insufficient for risk assessment. The aim of the current study was to analyze, in an animal model, transplacental genotoxicity, lipid peroxidation, and detoxification disturbances caused by the...

Impact of intrauterine development on health risks during adolescence and adulthood still needs to be investigated. The aim of study was to compare genome damage in newborns and mothers using the cytokinesis blocked micronucleus assay, nuclear division index (NDI), and centromere fluorescence in situ hybridization. The study was performed on 92 mot...

Purpose: Testicular seminoma cancer incidence has significantly increased over the last few decades, and although it is successfully treated by radiotherapy, long-term health risks are still unclear. The aim of the study was to show long-term genome damage in patients with seminoma after radiotherapy. Materials and methods: Chromosome aberration...

Puberty is the developmental window when the final maturation of body systems is orchestrated by hormones; lifelong sex-related differences and capacity to interact with the environment are defined during this life stage. Increased incidence in a number of chronic, multifactorial diseases could be related to environmental exposures during puberty:...

Social awareness of the need to preserve natural resources and energy efficiency politics has enabled a framework for the definition of sustainable building which can be realized by the introduction of new building materials and technologies. However, in some cases the use of new building materials and technologies can create microenvironments that...

From long-standing worries regarding the use of lead and asbestos to recent research into carcinogenic issues related to the use of plastics in construction, there is growing concern regarding the potential toxic effects of building materials on health. Toxicity of building materials provides an essential guide to this important problem and its sol...

Development of graphical/visual presentations of cancer etiology caused by environmental stressors is a process that requires combining the complex biological interactions between xenobiotics in living and occupational environment with genes (gene-environment interaction) and genomic and non-genomic based disease specific mechanisms in living organ...

The role of steroids in carcinogenesis has become a major concern in environmental protection, biomonitoring, and clinical research. Although historically oestrogen has been related to development of reproductive system, research over the last decade has confirmed its crucial role in the development and homeostasis of other organ systems. As a numb...

An increase in the incidence of breast cancer in women aged<40 years has been reported in recent years. Increased incidence could be partly explained by subtle detection biases, but the role of other risk factors cannot be ruled out. The purpose of the present study was to investigate the changes in temporal trends in breast cancer incidence in Eur...

Following complexity as a new approach in science of 21st century biomonitoring of biological effects caused by ionizing radiation received an option of a new dimension. Insight in biological response of mammals to ionizing radiation exposure by integration of genome, non-genome and distant organ bystander effects will significantly change evaluati...

Long-Term Follow-Up Study of Genome Damage Elimination in Patients with Testicular Seminoma Exposed to Ionising Radiation during Radiotherapy The rate of genome damage elimination after therapeutic exposure to ionising radiation was estimated in stage I testicular seminoma patients monitored over a seven-year follow-up. DNA damage elimination in pe...

Children may be more susceptible to the effects of the environmental exposure and medical treatments than adults; however, limited information is available about the differences in genotoxic effects in children by age, sex and health status. Micronucleus (MN) assay is a well established method of monitoring genotoxicity, and this approach is thorou...

Prenatal, Early Life, and Childhood Exposure to Genotoxicants in the Living Environment Health disorders and diseases related to environmental exposure in children such as cancer and immunologic disturbances (asthma, allergies) are on the rise. However, complex transplacental and prepubertal genotoxicology is given very limited consideration, even...

Complex exposure to xenobiotics is one of the reasons for the reported increase of respiratory diseases, cancer and immunological disturbances. Among such xenobiotics there are food mutagens whose effects on human health in the low level and/or chronic exposure still remains unknown. In the present manuscript, the compounds ethanol (EtOH), 4-hydrox...

Lung cancer is a dominant cause of cancer mortality. The etiology of lung cancer is mainly related to cigarette smoking, airborne genotoxic carcinogens, and arsenic, but its sex-specific incidence suggests that other mechanisms, such as hormones, may also be involved in the process of carcinogenesis. A number of agents commonly present in the livin...

Antiepileptic drugs (AED) as transplacental agents are known to have adverse effects on fetal development. Genotoxicity of AEDs is still not fully understood. The aim of present study was to investigate the transplacental genotoxicity of valproate on animal model and in 21 mothers and their newborns receiving AED. In both studies, in vivo micronucl...

Environmental xenoestrogens pose a significant health risk for all living organisms. There is growing evidence concerning the different susceptibility to xenoestrogens of developing and adult organisms, but little is known about their genotoxicity in pre-pubertal mammals. In the present study, we developed an animal model to test the sex- and age-s...