Manufacture of lead-containing products has long been associated with various health risks. To get an insight into the related genotoxic risks, we conducted a biomonitoring study in 50 exposed ...workers and 48 matched controls using a battery of endpoints that sensitively detect the extent of genome instability in peripheral blood lymphocytes. The levels of primary DNA damage were estimated with the alkaline comet assay, while cytogenetic abnormalities were determined with the cytokinesis-block micronucleus (CBMN) cytome assay. Additionally, CBMN slides of 20 exposed and 16 control participants were subjected to fluorescence
hybridisation (FISH), coupled with pancentromeric probes to establish the incidence of centromere-positive micronuclei, nuclear buds, and nucleoplasmic bridges. Blood lead levels (B-Pb) were measured with atomic absorption spectrometry. To further characterise cumulative effects of occupational exposure, we measured erythrocyte protoporphyrin (EP) concentrations and delta-aminolevulinic acid dehydratase (ALAD) activity in blood. We also assessed the influence of serum folate (S-folate) and vitamin B
(S-B12) on genome stability. Compared to controls, occupationally exposed workers demonstrated significantly higher B-Pb (298.36±162.07 vs 41.58±23.02), MN frequency (18.71±11.06 vs 8.98±7.50), centromere positive MN (C+ MN) (8.15±1.8 vs 3.69±0.47), and centromere negative MN (C- MN) (14.55±1.80 vs 4.56±0.89). Exposed women had significantly higher comet tail intensity (TI) and length (TL) than control women. Furthermore, workers showed a positive correlation between age and nuclear buds and MN, between MN and years of exposure, and between S-B
levels and TI and ALAD activity, while a negative correlation was found between TI and B-Pb. These findings suggest that occupational settings in the manufacture of lead-containing products pose significant genotoxic risks, which calls for developing more effective work safety programmes, including periodical monitoring of B-Pb and genetic endpoints.
The aim of study was to compare salivary and serum concentrations of interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with oral leukoplakia, oral ...cancer and healthy controls.
Eighty eight patients (28 with oral cancer, 29 leukoplakia, and 31 healthy controls) were included in this study. Cytokine concentrations were measured by commercial enzyme linked immunoassay.
Salivary IL-1β and IL-6 were significantly higher in oral cancer patients than in patients with leukoplakia and control group (p<0.05). No differences in concentrations of salivary TNF-α between either of the groups were observed. Serum concentrations of IL-1β were below level of detection in all but two participants. No significant differences between the groups were observed in serum concentrations of IL-6. Serum TNF-α was significantly higher in control subjects than in oral cancer patients.
Patients with oral cancer have elevated levels of inflammatory cytokines in their saliva. Whether this elevation can be used for monitoring the malignant transformation of oral leukoplakia remains to be answered by further follow up studies.
The nephrotoxic mycotoxin ochratoxin A (OTA), a common contaminant of cereals, has been implicated in the etiology of endemic nephropathy. It was also frequently found in low concentrations in blood ...of healthy populations in countries where endemic nephropathy is not known. However, data on regional and seasonal differences in the frequency and concentration of OTA in human blood are scarce. In June, September and December 1997, and March 1998, about 50 human blood samples were collected randomly from blood donors for blood banks in the Coatian cities of Osijek, Rijeka, Split, VaraZdin and Zagreb. OTA was measured in the total of 983 samples using an HPLC technique with fluorescent detection. The daily intake of OTA was estimated from the mean concentration found in different cities and at different times of year. Samples containing OTA above the detection limit (0.2 ng/ml of plasma) were found in populations from all Croatian cities at all collecting periods. The highest frequency (59%) of samples containing OTA above the detection limit and the highest mean concentration (0.39 ng/ml) were found in June. Both the frequency and the mean concentration were lowest in all samples in December (36% and 0.19 ng OTA/ml, respectively). Osijek was the city with the highest frequency of OTA-positive samples (81%) and the highest mean OTA concentration (0.56 ng/ml). The total mean concentration of OTA in blood of healthy population in Croatia is lower (0.30 ng/ ml) than the mean concentration in European countries as a whole (0.90 ng/ml). The estimated daily intake, calculated from the mean concentration in all blood samples, is 0.40 ng OTA/kg body weight, which is much lower than that proposed by World Health Organization as the tolerable daily intake (16.0 ng/kg body weight). Healthy populations of Croatia are exposed to low, but seasonally and regionally variable amounts of OTA.
Although it is known that platelet serotonin level (PSL) depends directly on platelet serotonin uptake (PSU) through the plasma membrane, reports on their interrelation are inconsistent. The aim of ...this study was to systematically explore the relationship between these two platelet serotonin parameters in large human population.
PSL and full-kinetics of PSU were determined on 318 blood donors (276 males, 42 females; 20–67
years).
The overall correlation coefficient between PSL and maximal velocity of PSU was highly significant but unexpectedly low (
r
=
0.269). Further analyses revealed lack of correlation among females, and variable association among males, depending on the subject age and season of measurements. Highly significant correlations were observed in spring–winter, while association was absent during summer–autumn. Lowering of PSL–PSU correlation with increased age was also demonstrated, showing modest interrelation among younger men and no interrelation in older population. By multiple regression analyses season was identified as the only independent predictor of PSL–PSU relationship.
The results show prominent influence of biological (sex, age) and, especially, environmental (seasons) physiology on the intraindividual relationship between PSL and PSU. Although serotonin transporter activity plays an important role in determining PSL, the observed correlations indicate that other factors may predominate.
Genome-wide association studies in patients with testicular germ-cell tumors (TGCT) from Great Britain and the United States have identified six susceptibility loci in or near biologically plausible ...candidate genes. However, these loci have not been replicated in an independent European sample. We performed a genetic replication study of previously identified TGCT susceptibility loci in a Croatian case-control sample and performed additional analyses as concerning histological subtypes or tumor staging. We analyzed six single-nucleotide polymorphisms rs2900333 (ATF7IP), rs210138 (BAK1), rs755383 (DMRT1), rs995030 (KITLG), rs4624820 (SPRY4), and rs4635969 (TERT/CLPTM1L), each representing one of the published susceptibility loci/genes. Five susceptibility loci were found to be also associated in the Croatian population with P-values between 2.1e-10 (rs995030; odds ratio OR 3.08) and 0.01739 (rs4635969; OR 1.37), which remained statistically significant after correction for multiple testing. Although rs2900333 near ATF7IP just showed borderline association with all-TGCT (OR 1.24, P = 0.062), it showed significant association with the more aggressive forms of the tumor (OR 1.51, P = 0.0067)-a clinically interesting finding, which however has to be replicated in an independent sample. Assessment of cumulative risks revealed that men with at least seven risk alleles have a more than 2.5-fold increased disease risk (OR = 2.73, 95% confidence interval = 1.98-3.79). In summary, we independently replicated the majority of TGCT susceptibility loci identified previously in a Croatian sample and suggested a possible role of genetic variation near ATF7IP in regulating disease progression.
Disturbances in serotonin (5HT) transmission are the most frequently reported neurobiological substrates of suicidal behavior. Because 5HT transporter plays a central role in the regulation of 5HT ...synaptic function and its gene contains two functional polymorphisms (5-HTTLPR in the promoter region and VNTR in the second intron), it represents an interesting candidate for association studies in suicidal behavior.
In this study, a possible association of 5-HTTLPR and intron 2-VNTR polymorphisms of the 5HT transporter gene with suicidal behavior was investigated in a sample of 135 suicide victims and 299 healthy control subjects of Croatian/southern Slavic origin.
There were no significant differences in 5-HTTLPR and intron 2-VNTR genotype- and allele- frequency distributions between suicide victims and healthy control subjects; however, a tendency toward an increase of 5-HTTLPR allele L and VNTR-allele 10 were observed in suicide group. Analysis of distribution of estimated haplotype frequencies revealed differences between suicide victims and control subjects, with an excess of haplotype L10 among suicide victims (
p = .0112).
Our results provide modest evidence for a possible association of the 5HT transporter gene with a completed suicide. Further studies are needed to determine whether alterations in 5HTt gene expression are involved in suicidal behavior.
Monoamine oxidase (MAO), a mitochondrial flavine containing enzyme, exists in two isoenzymes, MAO-A and MAO-B. Platelets contain MAO-B subtype, proposed to be a biomarker for different personality ...characteristics and vulnerability for substance abuse. The most common polymorphism of MAO-B gene, a single base change (A or G) occurs in intron 13. It has been proposed to be a functional polymorphism, controlling the activity of MAO-B in platelets. The aim of the study was to determine the association between platelet MAO-B activity and MAO-B intron 13 polymorphism in 225 racially and ethnically uniform healthy Caucasian men of the Croatian origin. Our results showed that platelet MAO-B activity did not differ between subjects subdivided into those with ≪A-allele≫ or ≪G-allele≫. This polymorphism of the MAO-B gene did not control the activity of the MAO-B in platelets. Platelet MAO-B activity was associated only with the smoking status, and it was significantly decreased in smokers when compared to nonsmokers. No significant association was found between MAO-B polymorphism and smoking status. In healthy individuals of the Croatian origin, the studied MAO-B polymorphism showed a lack of functional importance in regulating MAO-B activity in platelets. Since different populations may vary in the association between functional polymorphism and the MAO-B activity, and the genotype of transcription factor AP-2β was reported to be associated with altered platelet MAO-B activity, and with specific personality traits, further studies on different populations should be conducted to elucidate the molecular mechanism/s regulating platelet MAO-B activity.
Single nucleotide polymorphisms of TP53 gene in human populations are expected to cause perturbation of p53 function, and therefore could influence risk and/or progress of disease. There are ...differences in inducing apoptosis, cell cycle arrest, transcriptional activity, protein interactions between variants in codon 72 (Arg72Pro), although the association of polymorphism and risk of cancer is controversial. The aim of our study was to investigate the frequency of alleles and genotypes of Arg72Pro polymorphism in the ethnically homogenous Croatian population and to compare it with the worldwide populations. In a cohort of 576 participants the genotype frequencies of Arg/Arg, Arg/Pro and Pro/Pro are 54.34, 38.71 and 6.95 %, respectively. We statistically sorted the population of Croatia into the same group with other European populations and Caucasians from North America. This finding is important for the molecular pathways studies involved in disease as well as in pharmacogenetic studies. (doi:10.5562/cca1866) Keywords: tumor suppressor gene p53, p73, SNP, Arg72Pro
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