Antineoplastic Drugs as a Potential Risk Factor in Occupational Settings: Mechanisms of Action at the Cell Level, Genotoxic Effects, and Their Detection Using Different Biomarkers

U članku je prikazana osnovna podjela antineoplastičnih lijekova prema mehanizmima djelovanja na razini stanice. Objašnjeni su mehanizmi genotoksičnosti najvažnijih vrsta lijekova koji se primjenjuju u okviru uobičajenih protokola za liječenje zloćudnih novotvorina. Navedena je važeća klasifi kacija antineoplastika prema kancerogenom potencijalu, podaci o mutagenom potencijalu te je prikazana njihova podjela u skladu s anatomsko-terapijsko-kemijskim sustavom klasifi kacije. Sustavno su prikazani najvažniji rezultati svjetskih i hrvatskih istraživanja na populacijama radnika izloženih antineoplasticima, provedenih u razdoblju 1980.-2009. s pomoću četiri najčešće primjenjivane metode: analize izmjena sestrinskih kromatida, analize kromosomskih aberacija, mikronukleus-testa i komet-testa. Objašnjena su osnovna načela navedenih metoda te raspravljene njihove prednosti i nedostaci. Biološki pokazatelji daju važne podatke o individualnoj osjetljivosti profesionalno izloženih ispitanika koji mogu poslužiti unaprjeđenju postojećih uvjeta rada i upravljanju rizicima pri izloženosti genotoksičnim agensima. Na osnovi prednosti i nedostataka citogenetičkih metoda zaključeno je da je mikronukleus-test, koji podjednako uspješno dokazuje klastogene i aneugene učinke, jedna od najboljih metoda dostupnih za otkrivanje štetnih djelovanja antineoplastičnih lijekova koji su u aktivnoj primjeni.This article brings an overview of the mechanisms of action of antineoplastic drugs used in the clinical setting. It also describes the genotoxic potentials of the most important classes of antineoplastic drugs involved in standard chemotherapy protocols. Classifi cation of antineoplastic drugs according to the IARC monographs on the evaluation of carcinogenic risks to humans is accompanied by data on their mutagenicity and the most recent updates in the Anatomical Therapeutic Chemical (ATC) Classifi cation System. We report the main fi ndings of biomonitoring studies that were conducted in exposed healthcare workers all over the world between 1980 and 2009 using four biomarkers: sister chromatid exchanges, chromosome aberrations, micronuclei. and the comet assay. The methods are briefl y explained and their advantages and disadvantages discussed. Biomarkers provide important information on individual genome sensitivity, which eventually might help to improve current working practices and to manage the risks related with exposure to genotoxic agents. Taking into consideration all known advantages and drawbacks of the existing cytogenetic methods, the micronucleus assay, which is able to detect both clastogenic and aneugenic action, is the most suitable biomarker for assessing harmful effects of antineoplastic drugs currently used in health care

Measuring the effects of pesticides on occupationally exposed humans with the comet assay

In this study we examine the effects of a mixture of pesticides on occupationally exposed agricultural workers. The study was performed on 149 people, 84 agricultural workers and 65 healthy men from the same area, who served as the control group. The exposed group was divided into a subgroup with 65 individuals moderately exposed (39 men and 26 women) and a highly exposed subgroup consisted of 19 men. The statistical analysis of the comet assay results showed that there were no significant differences in basal DNA damage between pesticide-exposed workers and the control group nor between moderately and highly exposed ones. In addition, exposure of peripheral blood lymphocytes to hydrogen peroxide or 7-irradiation led to a similar degree of DNA damage and subsequent repair for all the studied populations. © 2006 Wiley Periodicals, Inc

Effects of pesticides on occupationally exposed humans

Pesticides are known to contain numerous genotoxic compounds; however, genotoxicity biomonitoring studies of workers occupationally exposed to pesticides have produced variable results. In this study, we employed the Comet assay to examine DNA damage in peripheral blood lymphocytes (PBLs) from 64 greenhouse workers from Almera in south-eastern Spain in comparison to PBLs from 50 men from the same area but not engaged in any agricultural work. The results indicated that there were no differences in the basal levels of DNA damage in the two study groups. In addition, exposure of PBL from the workers and controls to hydrogen peroxide or gamma-irradiation led to similar levels of DNA damage; the subsequent repair of the induced DNA damage was also similar for both study populations. Smoking had no impact on any of the responses. The results of this study indicate that the greenhouse workers had no detectable increase in DNA damage or alteration in the cellular response to DNA damage compared to our control population

Pathophysiologic factors of bronchial asthma in childhood

In this report we analyzed in detail asthma, which is a reactive airway disease, is a leading cause of chronic illness in childhood. Important pathophysiologic factors are the bronhoconstriction and inflammation. T lymphocytes, eosinophils, macrophages and neutrophils play a key role in the chronic inflammation of asthma. Airway hyperreactivity relates to the overall severity of the disease. The review addresses the benefits and risks of medications currently in use, such as adrenergic agonists, anticholinergics and glucocorticoids

Stress and the progression of HIV disease

The reciprocal interactions between the neuroendocrine, immune, and autonomic nervous system are complicated, yet worthy of examination. A body of literature suggests that psychological factors such as stress, or psychiatric conditions such as major depression, may influence the immune system thereby altering host susceptibility to viral, or other types of infection. The present article examines the role of stress in the progression of HIV disease. We refer to the immune system, to stress, HIV, psychosocial factors well as the impact of psychiatric conditions like depression. In particular, we discuss about the biological mediators of psychological status which can play an important role in mediating HIV disease progression. We evaluate the most recent literature within the context of this burgeoning field, taking into account some methodological problems that often arise. Some considerations for future research are also presented at the end. ©Pharmakon-Press

Serotonin and personality: How does serotonin relate to impulsivity and aggression?

The present article investigated the relationship between serotonin (5-HT) and personality. In particular, we examined the effect that serotonin has on impulsivity and aggression. Different neurotransmitters seem to affect different aspects of personality. The role of central serotonergic system in psychiatric disorders has been the main focus of research for more than two decades, mainly related to clinical depression. Aggression and impulsivity have been linked to dysregulation in central serotonergic systems. There is strong evidence that abnormalities in the central serotonergic system are involved in the pathogenesis of suicidal behaviour. We report the results of a series of neuroendocrine and post-mortem experiments, we also report studies which measure CSF serotonin metabolites, or use peripheral measures of 5-HT function. Genetic studies are also mentioned and criticism on the methodologies is made. The emerging picture is that a reduction in central 5-HT function is associated with a tendency toward impulsive aggressive behaviour in both animals and humans, which in turn is related to suicidal behaviour. ©Pharmakon-Press