Blood plasma levels of biomarkers of liver status and lipid profile among nail technicians occupationally exposed to low-level mixture of volatile organic compounds.

PURPOSE: Nail technicians (NTs) are exposed to a low-level mixture of volatile organic solvents (VOCs), yet the health hazards related to such exposure are unknown. This study thus aimed to compare the blood plasma levels of selected biomarkers related to liver status and lipid profile among occupationally exposed NTs and unexposed controls. Associations between out-of-normal-range levels of such biomarkers and occupational exposure to VOCs mixture have also been investigated. METHODS: The study enrolled 145 female NTs and 152 unexposed controls. Biochemical analyses were performed using spectrophotometric assays and obtained data were analyzed using general linear model and Poisson regression modelling adjusted to multiple confounders. RESULTS: Compared to controls, NTs presented significantly increased plasma activities of ALT (2.04 ± 0.63 ln-U/l vs. 1.25 ± 0.71 ln-U/l; p < 0.0001) and AST (2.73 ± 0.25 ln-U/l vs. 2.08 ± 0.95 ln-U/l; p < 0.0001), and significantly increased plasma levels of TG (4.38 ± 0.53 ln-mg/dl vs. 4.21 ± 0.42 ln-mg/dl; p < 0.05) and TC/HDL ratio (1.18 ± 0.36 vs. 1.02 ± 0.27; p < 0.0005). Plasma levels of HDL were significantly lower among NTs (4.02 ± 0.29 ln-mg/dl vs. 4.21 ± 0.26 ln-mg/dl; p < 0.0001). Moreover, NTs were found to present significantly increased risk of occurrence of clinically relevant plasma HDL levels below 3.91 ln-mg/dl (i.e., 50 mg/dl; RR = 1.58, 95% CI 1.07-2.32, p < 0.05), as well as increased risk of clinically relevant TC/HDL ratio above the normal range limit of 3.5 (RR = 1.68, 95% CI 1.19-2.35, p < 0.005), as compared to unexposed controls. CONCLUSION: Nail technicians are subject to adverse changes in selected plasma biomarkers related to liver functions, some of which may be of clinical relevance.

Longitudinal effect of phthalates exposure on allergic diseases in children.

BACKGROUND: Environmental chemicals, such as phthalates, phenols, and parabens, may affect children's immune development and contribute to the risk of atopic diseases and asthma. OBJECTIVE: To evaluate the associations between prenatal and childhood phthalate exposure and atopic diseases in children at the age of 9 years. METHODS: This analysis is restricted to 145 mother-child pairs from the prospective Polish Mother and Child Cohort Study. Phthalate metabolite levels were assessed in the urine samples collected from mothers during the third trimester of pregnancy and from children at age of 2 and 9 years. For the appropriate recognition of children's health status, a questionnaire was administered to the mothers and completed with information from the medical record of each child. The clinical examination was performed by a pediatrician/allergist in the presence of the mother or a relative. RESULTS: A higher urine concentration of mono-2-ethyl-5-oxohexyl phthalate increased the risk of food allergy in children at the age of 9 years (odds ratio [OR], 1.75; 95% CI, 1.19-2.57; P = .004) and decreased the risk of atopic dermatitis (OR, 0.49; 95% CI, 0.27-0.87; P = .02). For mono-2-ethyl-5-hydroxyhexyl phthalate, an increased risk of atopic dermatitis was observed (OR, 1.90; 95% CI, 1.18-3.05; P = .008). A higher urine concentration of mono-benzyl phthalate increased the risk of asthma in children (OR, 1.67; 95% CI, 1.08-2.58; P = .02), but the risk of asthma decreased when the concentration of mono-2-ethylhexyl phthalate was higher (OR, 0.64; 95% CI, 10.43-0.97; P = .04). CONCLUSION: Our study has not provided clear evidence of the negative effect of phthalate exposure during pregnancy and within the 9 years after birth on allergic diseases in children.

The role of antioxidants and 25-hydroxyvitamin D during pregnancy in the development of allergic diseases in early school-age children - Polish Mother and Child Cohort Study.

Purpose: Based on the available data, alterations of the antioxidant defense as well as the vitamin status in mothers may affect the prenatal process of lung and immune system development as a pathophysiological background of increased prevalence of allergic diseases. The primary aim of the current study was to assess the associations among cord blood concentrations of zinc (Zn); copper (Cu); selenium (Se); ß-carotene; and vitamin A, E, and D, and the occurrence of atopic dermatitis, food allergy, allergic rhinitis, and asthma in early school-age children. Methods: We evaluated 211 children, 7-9 years old, from the Polish Mother and Child Cohort Study. the women were interviewed during pregnancy to collect demographic and socioeconomic data, and the medical and reproductive history. At delivery, umbilical cord blood plasma was sampled. Seven to nine years after the birth, the child's exposure and health status (including skin-prick test and spirometry for allergy assessment and urine sample for cotinine level) were examined. In the analyses, a multivariable model was applied. Results: Statistically significant relationships were found among Zn; Cu; Se; and vitamin A, E, and D concentrations in cord blood; and the prevalence of food allergy, allergic rhinitis, atopic dermatitis, and asthma in children ages 7-9 years after adjustment for several confounders. Conclusion: We showed an imbalance in the antioxidant defense system in cord blood, which may lead to the occurrence of allergic diseases later in life. The maternal diet may have substantial potential to modify immune tolerance and, consequently, the development of allergic disease in the offspring.Clinical trial NCT01861548, www.clinicaltrials.gov.

Circadian Gene Polymorphisms Associated with Breast Cancer Susceptibility.

Breast cancer (BC) is a major problem for civilization, manifested by continuously increasing morbidity and mortality among women worldwide. Core circadian genes may play an important role in cancer development and progression. To evaluate the effects of single nucleotide polymorphism (SNP) in circadian genes in BC risk, 16 functional SNPs were genotyped in 321 BC patients and 364 healthy women using the TaqMan fluorescence-labelled probes or High-Resolution Melt Curve technique in the Real-Time PCR system. The selected SNPs were analyzed for the risk of BC, progression, and the influence on gene expression in BC tissue pairs to demonstrate the functionality of genetic variants. The study showed a relationship between an increased BC risk under the dominant genetic model of CRY2 rs10838524, PER2 rs934945, and recessive genetic model of PER1 rs2735611. A protective effect of BMAL1 rs2279287 was observed among carriers with at least one variant allele. Moreover, we found an increased risk of estrogen-/progesterone-positive tumors under the dominant genetic model of PER2 rs934945 and estrogen negative tumors under the variant genotype of CRY2 rs10838524, PER1 rs2735611. We demonstrated significantly altered gene expression of BMAL1, CRY2, PER1, PER2, PER3 according to particular genotypes in the BC tissue pairs. Our findings support the hypothesized role of circadian genes in breast carcinogenesis and indicate probable biomarkers for breast cancer susceptibility.

Micronutrients during pregnancy and child psychomotor development: Opposite effects of Zinc and Selenium.

Studies on the impact of micronutrient levels during different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the association between maternal plasma concentrations of selected micronutrients, such as: copper (Cu), zinc (Zn), selenium (Se), and child neuropsychological development. The study population consisted of 539 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL). The micronutrient levels were measured in each trimester of pregnancy, at delivery and in the cord blood. Psychomotor development was assessed in children at the age of 1 and 2 years using the Bayley Scales of Infant and Toddler Development. The mean plasma Zn, Cu and Se concentrations in the 1st trimester of pregnancy were 0.91±0.27mg/l, 1.98±0.57mg/l and 48.35±10.54µg/l, respectively. There were no statistically significant associations between Cu levels and any of the analyzed domains of child development. A positive association was observed between Se level in the 1st trimester of pregnancy and child language and motor skills (ß=0.18, p=0.03 and ß=0.25, p=0.005, respectively) at one year of age. Motor score among one-year-old children decreased along with increasing Zn levels in the 1st trimester of pregnancy and in the cord blood (ß=-12.07, p=0.003 and ß=-6.51, p=0.03, respectively). A similar pattern was observed for the association between Zn level in the 1st trimester of pregnancy and language abilities at one year of age (ß=-7.37, p=0.05). Prenatal Zn and Se status was associated with lower and higher child psychomotor abilities, respectively, within the first year of life. Further epidemiological and preclinical studies are necessary to confirm the associations between micronutrient levels and child development as well as to elucidate the underlying mechanisms of their effects.

Selenium status during pregnancy and child psychomotor development-Polish Mother and Child Cohort study.

BACKGROUND: The studies on the impact of selenium (Se) levels in different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the impact of prenatal Se on child neurodevelopment. METHODS: The study population consisted of 410 mother-child pairs from Polish Mother and Child Cohort. Se levels were measured in each trimester of pregnancy, at delivery, and in cord blood by graphite furnace atomic absorption spectrometry. Psychomotor development was assessed in children at the age of 1 and 2 y using the Bayley Scales of Infant and Toddler Development. RESULTS: Plasma Se levels decreased through pregnancy (from 48.3 ± 10.6 µg/l in the first trimester to 38.4 ± 11.8 µg/l at delivery; P < 0.05). A statistically significant positive association between Se levels in the first trimester of pregnancy and motor development (ß = 0.2, P = 0.002) at 1 y of age, and language development (ß = 0.2, P = 0.03) at 2 y of age was observed. The positive effect of Se levels on cognitive score at 2 y of age was of borderline significance (ß = 0.2, P = 0.05). CONCLUSION: Prenatal selenium status was associated with child psychomotor abilities within the first years of life. Further epidemiological and preclinical studies are needed to confirm the association and elucidate the underlying mechanisms of these effects.

Lipid peroxidation and glutathione peroxidase activity relationship in breast cancer depends on functional polymorphism of GPX1.

BACKGROUND: Since targeting oxidative stress markers has been recently recognized as a novel therapeutic target in cancer, it is interesting to investigate whether genetic susceptibility may modify oxidative stress response in cancer. The aim of this study was to elucidate whether genetic polymorphism in the antioxidant enzymes is associated with lipid peroxidation in breast cancer. METHODS: We conducted a study among Polish women, including 136 breast cancer cases and 183 healthy controls. The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium - an antioxidant trace element involved in cancer. Genotyping was performed using the Real Time PCR. Lipid peroxidation was expressed as plasma concentration of thiobarbituric acid reactive substances (TBARS) and measured with the spectrofluorometric method. Glutathione peroxidase activity was spectrophotometrically determined in erythrocytes (GPx1) and plasma (GPx3) by the use of Paglia and Valentine method. Spectrophotometric methods were employed to measure activity of cytosolic superoxide dismutase (SOD1) in erythrocytes (Beauchamp and Fridovich method) and ceruloplasmin (Cp) in plasma (Sunderman and Nomoto method). Plasma selenium concentration was determined using graphite furnace atomic absorption spectrophotometry. RESULTS: Breast cancer risk was significantly associated with GPX1 rs1050450 (Pro198Leu) polymorphism, showing a protective effect of variant (Leu) allele. As compared to the control subjects, lipid peroxidation and GPx1 activity were significantly higher in the breast cancer cases, whereas ceruloplasmin activity was decreased. After genotype stratification, both GPx1 activity and TBARS concentration were the highest in GPX1 Pro/Pro homozygotes affected by breast cancer. At the same time, there was a significant correlation between the level of lipid peroxidation and GPx1 activity among the cancer subjects possessing GPX1 Pro/Pro genotype (r = 0.3043; p = 0.0089), whereas such a correlation was completely absent in the cases carrying at least one GPX1 Leu allele as well as in the controls (regardless of GPX1 genotype). CONCLUSIONS: GPX1 polymorphism may be an important factor modifying oxidative stress response in breast cancer subjects. Further studies are needed to elucidate its potential clinical significance.

Today's oxidative stress markers.

Oxidative stress represents a situation where there is an imbalance between the reactive oxygen species (ROS) and the availability and the activity of antioxidants. This balance is disturbed by increased generation of free radicals or decreased antioxidant activity. It is very important to develop methods and find appropriate biomarkers that may be used to assess oxidative stress in vivo. It is significant because appropriate measurement of such stress is necessary in identifying its role in lifestyle-related diseases. Previously used markers of oxidative stress, such as thiobarbituric acid reactive substances (TBARS) or malondialdehyde (MDA), are progressively being supplemented by new ones, such as isoprostanes (IsoPs) and their metabolites or allantoin. This paper is focusing on the presentation of new ones, promising markers of oxidative stress (IsoPs, their metabolites and allantoin), taking into account the advantage of those markers over markers used previously.

Rad51C: a novel suppressor gene modulates the risk of head and neck cancer.

We conducted a case-control study to investigate the possible association between the head and neck cancer (HNC) and genetic variability of Rad51C tumor suppressor gene. Eight polymorphic sites spanning over non-coding regions of Rad51C promoter, exon 1 and intron 1 were genotyped in 81 HNC cases and 156 healthy controls using the real-time PCR technique. One investigated site turned out to be not polymorphic, while among the remaining seven sites a significant HNC risk-increasing effect was found for rs16943176 (c.-118G>A), rs12946397 (c.-26C>T) and rs17222691 (c.145+947C>T) on both allelic (OR=1.8; p<0.05) and genotypic (OR=2.0; p<0.05) level. Furthermore, our data seem to provide marginal evidence, that this effect might possibly be confined to women only (OR=2.8; p=0.05 for allelic and OR=3.7; p=0.05 for genotypic comparisons). These SNPs were found to co-segregate together forming two distinct, HNC risk-modulating haplotypes. The genetic variability of Rad51C might thus be of relevance with respect to HNC risk.

The role of zinc, copper, plasma glutathione peroxidase enzyme, and vitamins in the development of allergic diseases in early childhood: The Polish mother and child cohort study.

It has been hypothesized that the increase in allergic disorders may, in part, be a consequence of changing diet. The primary aim of this study was to assess the associations between occurrence of atopic dermatitis; food allergy; the incidence of wheeze inhaled glucocorticosteroid use in children during the 1st year of life; and cord blood concentrations of copper, zinc, vitamins (A and E), and glutathione peroxidase activity. We evaluated 240 1-year-old children from the Polish Mother and Child Cohort Study. Women were interviewed during pregnancy to collect demographic and socioeconomic data and medical and reproductive history. Exposure to tobacco constituents was assessed based on questionnaire data. At delivery, umbilical cord blood plasma was sampled. One year after the birth, the child's exposure and health status were examined. In the analyses a multivariable model was used. Higher zinc and copper concentrations in cord blood were associated with increased likelihood of wheezing in 1-year-old children. This effect was seen only among children exposed to tobacco smoke at home. We also showed significantly lower activity of glutathione peroxidase enzyme 3 in umbilical cord blood plasma of children with atopic dermatitis during the 1st year of life. There were no significant associations between vitamin A and E concentrations in plasma and children's health. We showed imbalance in the antioxidant defense system in cord blood, which may lead to development of atopic dermatitis or wheezing in infancy. The association between maternal nutrient status during pregnancy and child's health is complex and interacts with other environmental factors such as tobacco exposure. This study was a part of the clinical trial NCT01861548 registered at ClinicalTrials.gov.

Functional polymorphisms in the matrix metalloproteinase genes and their association with bladder cancer risk and recurrence: a mini-review.

Molecular pathogenesis of muscle invasive bladder cancer and non-muscle invasive bladder cancer is incompletely elucidated. It is believed that matrix metalloproteinases, which are involved in the processes of uncontrolled extracellular matrix substrates degradation and participate in modulating the activity of a variety of non-matrix proteins, can contribute to carcinogenesis. Polymorphisms in the MMP genes associated with unique genomic changes in bladder cancer patients are still being investigated to discover direct links with pathophysiological mechanisms. Because of the functional polymorphisms in the MMP genes, which have a proven or likely effect on their protein expression, they could possibly affect the tumor process. The current mini-review synthesizes findings regarding the association of genetic polymorphisms in the MMP genes with bladder cancer risk and recurrence in patients. We discuss the current views on the feasibility of genetic polymorphisms in the MMP1, 2, 3, 7, 8, 9 and 12 genes as a risk, and prognostic markers for patients with bladder cancer. The majority of the research described in the present mini-review proves that the genetic polymorphism in the MMP1 (rs1799750) is the most widely studied, and suggests that the rare genotype, 2G2G, of that gene might show increased susceptibility for bladder cancer, especially among smokers. However, existing statistically significant associations between the genetic polymorphisms in the MMP genes and bladder cancer risk have not been clearly shown, and further studies are necessary in order to positively confirm them or dispel potential false hopes.

Genetic polymorphisms in matrix metalloproteinases (MMPs) and tissue inhibitors of MPs (TIMPs), and bladder cancer susceptibility.

OBJECTIVES: To elucidate genetic polymorphisms of the matrix metalloproteinases (MMPs) MMP1 (rs1799750), MMP2 (rs243865), MMP9 (rs3918242), MMP12 (rs2276109) and tissue inhibitors of MMPs (TIMPs) TIMP1 (rs2070584) and TIMP3 (rs9619311) genes that may be involved in susceptibility to bladder cancer (BC). PATIENTS AND METHODS: We enrolled 241 patients with BC and 199 controls. Genomic DNA samples were extracted from peripheral blood and polymorphisms were analysed by high-resolution melting analysis and by real-time polymerase chain reaction using TaqMan fluorescent probes. RESULTS: Of the six evaluated polymorphisms of MMPs and TIMPs, only one was found to be associated with BC risk. There was a significant difference for MMP1 (rs1799750) 2G/1G+1G/1G genotype (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.39-0.98; P = 0.042). Additionally, there was a joint effect of this genotype on BC risk among 'ever smokers' (OR 0.51, 95% CI 0.28-0.89; P = 0.019), but not in 'never smokers'. The combined genotype MMP2 -1306C/T (rs243865) allele T with MMP9 -1562C/T (rs3918242) allele T was found to increase BC risk (OR 2.00, 95% CI 1.10-3.62; P = 0.022). CONCLUSIONS: Our results suggest that genetic variations in five polymorphisms of MMPs and TIMPs are not associated with a high risk of BC. Only MMP1 polymorphism may be related to the risk of BC, notably in 'ever smokers'. Our study suggests that the effects of polymorphisms of MMPs and TIMPs on BC risk deserve further investigation.

Exposure to polycyclic aromatic hydrocarbons in women from Poland, Serbia and Italy--relation between PAH metabolite excretion, DNA damage, diet and genotype (the EU DIEPHY project).

Exposure of the general population to polycyclic aromatic hydrocarbons (PAH) is ubiquitous. The aim of this study was to analyze biomarkers associated with the uptake of PAH in 428 non-smoking women from Lodz (Poland), Viterbo (Italy), Belgrade (Serbia) and from the Pancevo area, where the petrochemical complex was destroyed by the air raids in 1999. Urinary excretion of PAH metabolites was lowest in Italian women, intermediary for Serbian and highest in Polish women, who predominantly excreted hydroxy phenanthrenes as metabolites of phenanthrene. Bulky DNA adduct levels were highest in Italian and Polish women. Genotype or PAH ambient air levels could not explain the dissimilarities between the study groups with respect to biomarker patterns, which probably reflected differences in life style-associated factors.

Relationship between intensity of night shift work and antioxidant status in blood of nurses.

PURPOSE: Light-at-night exposure can disrupt the human circadian rhythm via clock gene expressions. The circadian rhythm influences antioxidant enzymes' activity and cellular mRNA levels of these enzymes. The employees working based on a shift system adjust to the changes occurring both on the cell level and on the level of the whole organism. Therefore, a question should be answered whether shift work disturbs oxidant-antioxidant balance and/or generates oxidative stress. METHODS: A cross-sectional study was conducted among nurses selected from the Local Registry of the Chamber of Nurses and Midwives in Lodz: 359 nurses worked daily only and 349 working rotating night shifts. These two groups differed significantly in respect of age (p < 0.0001), menopausal status (p < 0.0001), and current smoking habit (p = 0.02). The average total work duration was significantly shorter (12.4 years) in nurses working currently rotating night shifts who worked significantly longer on night shifts than day-workers (26.6 years). RESULTS: We found statistically significant higher red blood cell glutathione peroxidase in nurses working on night shifts (21.0 ± 4.6 vs. 20.0 ± 5.0 U/g Hb, p < 0.009) after adjusting for age, oral contraceptive hormone use, smoking, and drinking alcohol during last 24 h. Statistically significant lower vitamin A and E levels were found in the premenopausal women working in rotating system (0.690 ± 0.238 vs. 0.786 ± 0.262 µg/ml, p < 0.0001 for vitamin A and 10.93 ± 4.15 vs. 12.78 ± 4.75 µg/ml, p < 0.0001 for vitamin E). The marker of lipid peroxidation (TBARS concentration) was significantly lower in the premenopausal nurses than postmenopausal ones working day shifts only (2.06 ± 0.76 vs. 2.21 ± 0.80 nmol/ml, p < 0.038). We observed that erythrocyte GSH-Px activity rose statistically significant in nurses working more night shifts per month (p < 0.01). CONCLUSIONS: The results quoted above seem to support the existence of an association between light-at-night exposure and blood glutathione peroxidase activity in female shift workers. Nevertheless, in order to explain the mechanisms of this association, we need more studies.

The Effects of Two Kinds of Dietary Interventions on Serum Metabolic Profiles in Haemodialysis Patients.

The goal of this study was to evaluate the effects of two kinds of 24-week dietary interventions in haemodialysis patients, a traditional nutritional intervention without a meal before dialysis (HG1) and implementation of a nutritional intervention with a meal served just before dialysis (HG2), in terms of analysing the differences in the serum metabolic profiles and finding biomarkers of dietary efficacy. These studies were performed in two homogenous groups of patients (n = 35 in both groups). Among the metabolites with the highest statistical significance between HG1 and HG2 after the end of the study, 21 substances were putatively annotated, which had potential significance in both of the most relevant metabolic pathways and those related to diet. After the 24 weeks of the dietary intervention, the main differences between the metabolomic profiles in the HG2 vs. HG1 groups were related to the higher signal intensities from amino acid metabolites: indole-3-carboxaldehyde, 5-(hydroxymethyl-2-furoyl)glycine, homocitrulline, 4-(glutamylamino)butanoate, tryptophol, gamma-glutamylthreonine, and isovalerylglycine. These metabolites are intermediates in the metabolic pathways of the necessary amino acids (Trp, Tyr, Phe, Leu, Ile, Val, Liz, and amino acids of the urea cycle) and are also diet-related intermediates (4-guanidinobutanoic acid, indole-3-carboxyaldehyde, homocitrulline, and isovalerylglycine).

Cytotoxic effects in 3T3-L1 mouse and WI-38 human fibroblasts following 72 hour and 7 day exposures to commercial silica nanoparticles.

The potential toxic effects in murine (3T3-L1) and human (WI-38) fibroblast cell lines of commercially available silica nanoparticles (NPs), Ludox CL (nominal size 21 nm) and CL-X (nominal size of 30 nm) were investigated with particular attention to the effect over long exposure times (the tests were run after 72 h exposure up to 7 days). These two formulations differed in physico-chemical properties and showed different stabilities in the cell culture medium used for the experiments. Ludox CL silica NPs were found to be cytotoxic only at the higher concentrations to the WI-38 cells (WST-1 and LDH assays) but not to the 3T3-L1 cells, whereas the Ludox CL-X silica NPs, which were less stable over the 72 h exposure, were cytotoxic to both cell lines in both assays. In the clonogenic assay both silica NPs induced a concentration dependent decrease in the surviving fraction of 3T3-L1 cells, with the Ludox CL-X silica NPs being more cytotoxic. Cell cycle analysis showed a trend indicating alterations in both cell lines at different phases with both silica NPs tested. Buthionine sulfoximine (γ-glutamylcysteine synthetase inhibitor) combined with Ludox CL-X was found to induce a strong decrease in 3T3-L1 cell viability which was not observed for the WI-38 cell line. This study clearly indicates that longer exposure studies may give important insights on the impact of nanomaterials on cells. However, and especially when investigating nanoparticle effects after such long exposure, it is fundamental to include a detailed physico-chemical characterization of the nanoparticles and their dispersions over the time scale of the experiment, in order to be able to interpret eventual impacts on cells.

Night shift work characteristics and 6-sulfatoxymelatonin (MT6s) in rotating night shift nurses and midwives.

OBJECTIVES: Synthesis of melatonin follows a circadian cycle, with high melatonin levels during the night and low levels during the day. Light exposure at night has been hypothesised as one of potential mechanisms of breast carcinogenesis in the night shift workers through inhibition of melatonin synthesis. The aim of the study was to examine a number of determinants for night shift work in relation to 6-sulfatoxymelatonin (MT6s), primary melatonin metabolite. METHODS: The cross-sectional study included 354 nurses and midwives (aged 40-60 years) currently working on rotating night shifts and 370 working days only. Data from questionnaires and 1-week diaries were used to characterise current job and total occupational history. Associations between rotating night shift work characteristics and MT6s (creatinine adjusted) in spot morning urine were tested in multiple linear regression models. RESULTS: No significant differences were found for MT6s concentrations between women currently working on rotating night shifts and those working only day shifts (means 47.2 vs 45.7 ng/mg Cr, respectively). The adjusted means among rotating night shift nurses and midwives varied depending on the department of employment, from 35.1 ng/mg Cr in neonatology to 68.2 ng/mg Cr in the orthopaedics department. Women working eight or more night shifts per month had significantly lower MT6s levels than those having fewer night shifts per month (37.9 vs 47.4 ng/mg Cr, respectively). Total night shift work history was not associated with MT6s. CONCLUSIONS: The results of this study indicate that working eight or more night shifts per month may disrupt the synthesis of melatonin.

Detection of acetaldehyde derived N(2)-ethyl-2'-deoxyguanosine in human leukocyte DNA following alcohol consumption.

Epidemiological studies have shown an association between alcohol (ethanol) consumption and increased cancer risk. The effect of alcohol consumption on the levels and persistence of N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dG) formed by acetaldehyde, the oxidative metabolite of ethanol, in human leukocyte DNA was investigated. DNA was isolated from venous blood samples obtained from 30 male non-smoking individuals before consumption of alcohol (0h) and subsequently at 3-5h following the consumption of 150mL of vodka (containing 42% pure ethanol). Additional samples were collected 24h and 48h post-alcohol consumption. The levels of N(2)-ethyl-2'-deoxyguanosine (N(2)-ethyl-dG) in the DNA were determined following reduction of N(2)-ethylidene-dG with sodium cyanoborohydride using a liquid chromatography-tandem mass spectrometry selected reaction monitoring method. A slight time-dependent trend showing an increase and decrease in the levels of N(2)-ethyl-dG was observed following consumption of alcohol compared to time 0h, however, the differences were not statistically significant. The average levels of N(2)-ethyl-dG observed at 0h, 3-5h, 24h and 48h time points following ingestion of alcohol were 34.6±21.9, 35.1±21.0, 36.8±20.7 and 35.6±21.1 per 10(8) 2'-deoxynucleosides, respectively. In conclusion, alcohol consumption that could be encountered under social drinking conditions, does not significantly alter the levels of the acetaldehyde derived DNA adduct, N(2)-ethyl-dG in human leukocyte DNA from healthy individuals.

Lipidomic profiles as a tool to search for new biomarkers.

Lipidomics belongs to the family of the so-called omics domains, which, based on modern chemical technologies, strive to explain the biological principles of the organism's functioning. Main biological functions of lipids include energy storage, the formation of cell membranes, and participation in the transmission of biological signals, and their dysregulation is responsible for the development of pathological states. Thanks to lipid profiling, potential biomarkers for disease diagnosis and prognosis can be identified. This paper discusses selected examples of the use of lipidomic tests in the diagnosis of the kidney, metabolic and neoplastic diseases based on research papers published over the last few years (since 2016). Only works based on the study of human biological material by mass spectrometry methods were taken into account. The examples of lipidomics application presented in this publication are only a few of the possibilities of this technique. As potential possibilities have already been discovered, the next step for the research community is to work on standardization of the approach to lipidomic research and to develop bioinformatics methods that allow efficient processing and analysis of large amounts of data generated in this technique. Int J Occup Med Environ Health. 2022;35(2):111-26.