Aleksandra Fučić

The correlation between the frequency of micronuclei and specific chromosome aberrations in human lymphocytes exposed to microwave radiation in vitro

Human whole-blood samples were exposed to continuous microwave radiation, frequency 7.7 GHz, power density 0.5, 10 and 30 mW/cm2 for 10, 30 and 60 min. A correlation between specific chromosomal aberrations and the incidence of micronuclei after in vitro exposure was observed. In all experimental conditions, the frequency of all types of chromosomal aberrations was significantly higher than in the control samples. In the irradiated samples the presence of dicentric and ring chromosomes was established. The incidence of micronuclei was also higher in the exposed samples. The results of the structural chromosome aberration test and of the micronucleus test were comparatively analyzed. The values obtained showed a positive correlation between micronuclei and specific chromosomal aberrations (acentric fragments and dicentric chromosomes). The results of the study indicate that microwave radiation causes changes in the genome of somatic human cells and that the applied tests are equally sensitive for the detection of the genotoxicity of microwaves.

Environmental exposure to xenoestrogens and oestrogen related cancers: reproductive system, breast, lung, kidney, pancreas, and brain

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 number of anthropogenic agents are xenoestrogens, environmental health research has focused on oestrogen receptor level disturbances and of aromatase polymorphisms. Oestrogen and xenoestrogens mediate critical points in carcinogenesis by binding to oestrogen receptors, whose distribution is age-, gender-, and tissue-specific. This review brings data about cancer types whose eatiology may be found in environmental exposure to xenoestrogens. Cancer types that have been well documented in literature to be related with environmental exposure include the reproductive system, breast, lung, kidney, pancreas, and brain. The results of our data mining show (a) a significant correlation between exposure to xenoestrogens and increased, gender-related, cancer risk and (b) a need to re-evaluate agents so far defined as endocrine disruptors, as they are also key molecules in carcinogenesis. This revision may be used to further research of cancer aetiology and to improvement of related legislation. Investigation of cancers caused by xenoestrogens may elucidate yet unknown mechanisms also valuable for oncology and the development of new therapies.

Puberty dysregulation and increased risk of disease in adult life: possible modes of action.

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: however, insight on the susceptibility of the peripubertal period is still limited. The estrogen/androgen balance is a crucial axis in harmonizing the whole pubertal development, pointing out the significance of exposures to endocrine disruptors. Besides the reproductive system, endocrine-related perturbations may affect the maturation of skeleton, adipose tissues, brain, immune system, as well as cancer predisposition. Thus, risk assessment of environmental stressors should duly consider specific aspects of the pubertal window. Besides endocrine-related mechanisms, suggested research priorities include signaling molecules (e.g., kisspeptins, dopamine) as xenobiotic targets and disturbances of specific pubertal methylation processes potentially involved in neurobehavioral disorders and cancer risk in adulthood.

Chromosome aberrations in peripheral blood lymphocytes from control individuals

This study emphasizes the problems encountered in obtaining suitable control levels for comparison with occupational studies of exposure to clastogens. Blood samples taken from 135 individuals (69 females and 66 males) were examined for chromosome aberrations. The data include 15,368 cells scored for chromosome aberrations. The frequencies of chromatid and chromosome breaks, acentric fragments and dicentrics were determined. The frequency of the most common chromosome aberration, chromosome breaks, was 1.1 x 10(-2) and for dicentrics 0.26 x 10(-3). The values obtained were investigated in relation to sex, cigarette smoking habits, diagnostic X-ray exposure and use of antibiotics. In all the parameters, no significant differences were found.

The rate of elimination of chromosomal aberrations after accidental exposure to microwave radiation

Abstract Analysis of structural chromosome aberrations was performed in a group of radar station personnel who were engaged in repairing radar devices a couple of days earlier. Test results showed a major decline from the values recorded by regular mutagenic monitoring in terms of a significantly increased number of chromosome breaks, acentric fragments, dicentric and polycentric chromosomes with accompanying fragments, ring chromosomes and chromatid interchange. Multiply repeated mutagenic testing demonstrated for all subjects a fall in the total number of chromosome aberrations as a function of time. During a 30-week-long follow-up study a decrease in the total number of chromosome aberrations was observed. In the same period the presence of unstable aberrations such as dicentrics and ring chromosomes persisted, together with a relatively unchanged incidence of stable aberrations.

X-rays, microwaves and vinyl chloride monomer: their clastogenic and aneugenic activity, using the micronucleus assay on human lymphocytes

Chromosome aberration assays, sister-chromatid exchange techniques and micronucleus assays are commonly used methods for biomonitoring genetic material damaged by chemical or physical agents. On the other hand, their aneugenic activity, which can lead to hypoploidy and may also be associated with carcinogenesis, has not been thoroughly investigated. In our study we chose the micronucleus assay with a new mathematical approach to separate clastogenic from aneugenic activity of three well-known mutagens (vinyl chloride monomer, X-rays and microwaves) on the genome of human somatic cells. The comparison of frequencies of size distribution of micronuclei in the lymphocytes of humans exposed to each of these three mutagens showed that X-rays and microwaves were preferentially clastogens while vinyl chloride monomer showed aneugenic activity as well. Microwaves possess some mutagenic characteristics typical of chemical mutagens.

Mutagenicity of vinyl chloride in man: comparison of chromosome aberrations with micronucleus and sister-chromatid exchange frequencies.

The mutagenic effects of vinyl chloride monomer in man were studied in the lymphocyte culture with 3 methods: the chromosome aberration assay, the micronucleus assay and the sister-chromatid exchange method. Compared with control, values obtained by these tests are increased in workers occupationally exposed to vinyl chloride. In relation to non-smokers, smokers exposed to vinyl chloride show significant increases in sister-chromatid exchange frequencies. The problem of correlating the results of the chromosome aberration assay with micronucleus and sister-chromatid exchange frequencies is discussed.

PRENATAL, EARLY LIFE, AND CHILDHOOD EXPOSURE TO GENOTOXICANTS IN THE LIVING ENVIRONMENT

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 though intrauterine development and early childhood may be critical for elucidating the cancer aetiology. The foetus is transplacentally exposed to contaminants in food and environment such as various chemicals, drugs, radiochemically contaminated water and air. Target organs of xenobiotic action may differ between the mother and the foetus due to specific stage of developmental physiology and enzyme distribution. This in turn may lead to different levels of clastogenic and aneugenic metabolites of the same xenobiotic in the mother and the foetus. Adults protective behaviour is not sufficient to isolate children from radioisotopes, pesticides, toxic metals and metalloids, environmental tobacco smoke, endocrine disrupting chemicals, and various food contaminants, which are just a part of the stressors present in a polluted environment. In order to improve legislation related to foetus and child exposure to genotoxic and possibly carcinogenic agents, oncologists, paediatricians, environmental health specialists, and genotoxicologists should work together much more closely to make a more effective use of accumulated scientific data, with the final aim to lower cancer incidence and mortality. Izloženost genotoksičnim agensima iz životnog okoliša tijekom prenatalnog razvoja i djetinjstva Unatoč velikim naporima da se smanji okolišna izloženost u djece se dalje bilježi trend porasta pojavnosti karcinoma i imunosnih poremećaja (astma, alergije). Premda su intrauterini razvoj i rano djetinjstvo kritično razdoblje za tumačenje etiologije nastanka karcinoma, transplacentalna i prepubertetna genotoksikologija do danas su slabo istražene. Fetus je transplacentalno izložen brojnim fizikalnim i kemijskim čimbenicima: kontaminantima iz hrane i okoliša, radiokemijski kontaminiranoj vodi, zraku te lijekovima. Ciljna tkiva za djelovanje ksenobiotika mogu biti različita u majke i fetusa zbog različitosti u razvojnoj fiziologiji i distribuciji enzima. Zbog toga u organizmu majke i fetusa mogu nastati različite razine klastogenih i aneugenih metabolita istog ksenobiotika. Zaštitna uloga odraslih u namjeri da spriječe negativne utjecaje onečišćenog okoliša na djetetovo zdravlje često je ograničena jer su radioizotopi, olovo, PCB, pasivno pušenje, živa, endokrino aktivne tvari, pesticidi i kontaminanti prisutni u svim životnim područjima tijekom razvoja i rasta djeteta. Kako bi se poboljšalo zakonodavstvo vezano uz izloženost djece genotoksičnim i vjerojatno kancerogenim tvarima, tijekom razvoja potrebna je bolja suradnja onkologa, pedijatara, stručnjaka zdravstvene ekologije i genotoksikologa. Na taj način ostvarilo bi se uspješnije iskorištavanje postojećih znanstvenih podataka u cilju smanjenja incidencije karcinoma i mortaliteta.

A nine-year follow up study of a population occupationally exposed to vinyl chloride monomer

The presence of structural chromosome aberrations and sister chromatid exchange frequencies (SCE) were studied in lymphocytes from 28 male subjects occupationally exposed to vinyl chloride monomer for a period of 9 years. A significant increase in chromosomal damages and elevated SCE frequencies was detected during the third and fourth year of the follow-up study. During the last 2 years, all examined parameters are approaching control values. This is a result of decreasing vinyl chloride monomer concentrations in the working environment without interrupting the working process.

The value of cytogenetic monitoring versus film dosimetry in the hot zone of a nuclear power plant.

Cytogenetic analysis was carried out in 41 workers prior to and following regular maintenance work in a nuclear power plant. Although film dosimetry did not show the maximal annual permitted dose in any of the examined subjects, cytogenetic analysis carried out following the work detected dicentric chromosomes in peripheral blood lymphocytes of 20 workers. According to our findings smoking habits and previous exposure to ionizing radiation had no effect on the increased number of chromosomal aberrations.