Genotoxicity of source, treated and distributed water from four drinking water treatment plants supplied by surface water in Sardinia, Italy.

High levels of disinfection by-products (DBPs) are constantly found in drinking water distributed in Sardinia, an Italian island with a tourist vocation and critical issues related to the drinking water supply. To reduce the concentration of trihalomethanes the disinfectant in use was changed - chlorine dioxide was adopted instead of hypochlorite. However, this caused the appearance of other DBPs (e.g., chlorites) in water distributed to the population. Thus, the use of monochloramine as a secondary disinfectant (associated with chlorine dioxide as the primary disinfectant) was evaluated in four drinking water treatment plants supplied by artificial basins located in the central-northern part of Sardinia. Raw, disinfected and distributed waters were studied for genotoxicity using a battery of in vitro tests on different cells (bacteria, plant and mammalian cells) to detect different genetic endpoints (i.e., point and chromosome mutations and DNA damage). Moreover, a chemical and microbiological characterisation of water samples was performed. All samples of water distributed to the people showed mutagenic or genotoxic effects in different cells/organisms. In particular, chromosome aberrations in plant cells and DNA damage in human cells were observed. In this study, the use of chloramines associated with other disinfectants did not eliminate the mutagenicity present in the raw water and when the raw water was not mutagenic it introduced mutagenic/genotoxic substances. A careful management of drinking water is needed to reduce health hazards associated with the mutagenicity of drinking water.

Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach.

OBJECTIVES: Recently published works showed that occupational exposure to antineoplastic drugs (ANPD) is still frequent in hospital settings, despite significant safety policy improvements. The aim of this study was to assess the current level of occupational exposure to ANPD and any potentially associated cytogenetic damages in hospital nurses routinely handling ANPD. METHODS: Occupationally ANPD-exposed (n = 71) and ANPD-unexposed (n = 77; control) nurses were recruited on a voluntary basis from five hospitals in Northern and Central Italy. Evaluation of surface contamination and dermal exposure to ANPD was assessed by determining cyclophosphamide (CP) on selected surfaces (wipes) and on exposed nurses' clothes (pads). The concentration of unmetabolized CP­as a biomarker of internal dose­was measured in end-shift urine samples. Biomonitoring of genotoxic effects (i.e., biological effect monitoring) was conducted by analyzing micronuclei (MN) and chromosome aberrations (CA) in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e., glutathione S-transferases) were analyzed as well. RESULTS: We observed a significant increase in MN frequency (5.30 ± 2.99 and 3.29 ± 1.97; mean values ± standard deviation; p < 0.0001) in exposed nurses versus controls, as well as in CA detection (3.30 ± 2.05 and 1.84 ± 1.67; p < 0.0001), exposed subjects versus controls. Our results provide evidence that, despite safety controlled conditions, ANPD handling still represents a considerable genotoxic risk for occupationally exposed personnel. CONCLUSIONS: Because both MN and CA have been described as being predictive of group-increased cancer risk, our findings point to a need for improving specific safety procedures in handling and administering ANPD.

Primary DNA damage in welders occupationally exposed to extremely-low-frequency magnetic fields (ELF-MF).

BACKGROUND: Electric arc welding is known to involve considerable exposure to extremely-low-frequency magnetic fields (ELF-MF; 50 Hz). The aim of the present study was to evaluate individual exposure to ELF-MF during arc welding and to assess the eventually associated genotoxic hazard by evaluating primary DNA damage. METHODS: The study group comprised 21 electric arc welders (exposed) and 21 non-exposed control subjects (healthy blood donors). Occupational exposure to ELF-MF was measured using personal dosimeters worn during one complete work-shift (7 am to 5 pm). The extent of primary DNA damage was measured in peripheral blood leukocytes with the standard procedure of the alkaline comet assay. RESULTS: Tail length showed to have similar values in welders and controls. Whereas, the data showed a significant decrease for tail intensity (p = 0.01) and tail moment (p = 0.02) counts in exposed subjects compared to controls. CONCLUSIONS: The different results of our present study and published investigations from other research groups reporting positive results in the comet assay might be a result of different chromium and/or nickel (or other metals) exposure levels, which lead to DNA-protein cross-links at lower concentrations and DNA single-strand breakages at higher concentrations. Since these results are derived from a small-scale pilot study, a larger scale study should be undertaken.

Investigation of the cytotoxic, genotoxic, and apoptosis-inducing effects of estragole isolated from fennel (Foeniculum vulgare).

The present study was undertaken to evaluate, in the HepG2 human hepatoma cell line, the in vitro cytotoxic, genotoxic, and apoptotic activities of estragole (1), contained in the essential oil of Foeniculum vulgare (fennel) and suspected to induce hepatic tumors in susceptible strains of mice. Toward this end, an MTT cytotoxicity assay, a trypan blue dye exclusion test, a double-staining (acridine orange and DAPI) fluorescence viability assay, a single-cell microgel-electrophoresis (comet) assay, a mitochondrial membrane potential (Δψm) assay, and a DNA fragmentation analysis were conducted. In terms of potential genotoxic effects, the comet assay indicated that estragole (1) was not able to induce DNA damage nor apoptosis under the experimental conditions used.

A novel black poplar propolis extract with promising health-promoting properties: focus on its chemical composition, antioxidant, anti-inflammatory, and anti-genotoxic activities.

Propolis is a resinous mixture produced by honeybees which has been used since ancient times for its useful properties. However, its chemical composition and bioactivity may vary, depending on the geographical area of origin and the type of tree bees use for collecting pollen. In this context, this research aimed to investigate the total phenolic content (using the Folin-Ciocalteu assay) and the total antioxidant capacity (using the FRAP, DPPH, and ABTS assays) of three black poplar (Populus nigra L.) propolis (BPP) solutions (S1, S2, and S3), as well as the chemical composition (HPLC-ESI-MSn) and biological activities (effect on cell viability, genotoxic/antigenotoxic properties, and anti-inflammatory activity, and effect on ROS production) of the one which showed the highest antioxidant activity (S1). The hydroalcoholic BPP solution S1 was a prototype of an innovative, research-type product by an Italian nutraceutical manufacturer. In contrast, hydroalcoholic BPP solutions S2 and S3 were conventional products purchased from local pharmacy stores. For the three extracts, 50 phenolic compounds, encompassing phenolic acids and flavonoids, were identified. In summary, the results showed an interesting chemical profile and the remarkable antioxidant, antigenotoxic, anti-inflammatory and ROS-modulating activities of the innovative BPP extract S1, paving the way for future research. In vivo investigations will be a possible line to take, which may help corroborate the hypothesis of the potential health benefits of this product, and even stimulate further ameliorations of the new prototype.

[Evaluation of genotoxic effects in subjects occupationally exposed to antineoplastic drugs]. / Valutazione di effetti genotossici in soggetti con esposizione occupazionale a chemioterapici antiblastici.

The present molecular epidemiology study was carried out to evaluate the genotoxic effects of occupational exposure to antineoplastic drugs (ANP). The study was conducted in 52 hospital workers involved in the preparation, handling or administration of ANP in a hospital in Perugia (central Italy) and in 52 non-exposed control subjects matched for age, gender and smoking habits to the exposed subjects. Both comet assay and the micronucleus test were used to evaluate genome damage in peripheral blood lymphocytes in study subjects. The extent of primary DNA damage, as evaluated by the comet assay, was significantly increased in exposed personnel with respect to matched controls. On the other hand, no significant differences in micronuclei frequency was observed between the two groups. Multivariate linear regression analysis showed an association between years of occupational exposure over 10 years and higher extent of primary DNA damage in the exposed group. The results of this study confirm that handling ANP without appropriate precautions carries a genotoxic risk for exposed healthcare workers. These results address the need for regular biological effect monitoring of staff occupationally-exposed to ANP.

Effect of Cooking and Domestic Storage on the Antioxidant Activity of Lenticchia di Castelluccio di Norcia, an Italian PGI Lentil Landrace.

The aim of this work was to characterise Lenticchia di Castelluccio di Norcia (an Italian PGI lentil landrace) and assess the impact of cooking and storage on antioxidant activity. After opening the package (T0), samples were analysed using a set of chemical assays (i.e., total phenolic content, DPPH, ABTS, and ORAC assays). Analyses were also conducted on boiled, pressure-cooked, and 6-month-stored (T1) products. At both T0 and T1, raw Lenticchia di Castelluccio di Norcia PGI showed higher total phenolic content (T0: 9.08 mg GAE/g, T1: 7.76 mg GAE/g) and antioxidant activity (DPPH T0: 33.02 µmol TE/g, T1: 29.23 µmol TE/g; ABTS T0: 32.12 µmol CE/g, T1: 31.77 µmol CE/g; ORAC T0: 3.58 µmol TE/g, T1: 3.60 µmol TE/g) than boiled and pressure-cooked samples. Overall, pressure-cooking led to a smaller decline in total phenolic content and antioxidant activity than the common boiling procedure. Domestic storage led to a significant reduction in total phenolic content-both in raw and cooked products-but not in antioxidant activity. In summary, these results highlighted interesting amounts of phenols and antioxidant properties of this product, showing the impact of routine procedures. Given the relevance of pulses as sustainable plant-based meat alternatives and their importance in the prevention of non-communicable diseases, health professionals should consider these aspects in the context of correct nutrition education and scientific communication.

In vitro toxicological assessment of PhSeZnCl in human liver cells.

Phenylselenenylzinc chloride (PhSeZnCl) is an air-stable selenolate, easily synthesizable through oxidative insertion of elemental zinc into the Se-halogen bond of the commercially available phenylselenyl chloride. PhSeZnCl was shown to possess a marked GPx-like activity both in NMR and in vitro tests, and to effectively react with cellular thiols, and was supposed for a potential use in the chemotherapy of drug-resistant cancers. However, activity of PhSeZnCl in hepatic cells has never been tested before now. In this in vitro approach, we evaluated the cytotoxic, genotoxic, and apoptotic activities, as well as the effects on cell cycle of PhSeZnCl in two preclinical hepatic models, namely HepG2 and HepaRG cells. Results showed that cell viability of HepG2 and HepaRG cells decreased in a dose-dependent manner, with a more marked effect in HepG2 tumour cells. Moreover, treatment with 50 µg/mL PhSeZnCl caused an increase of primary DNA damage (4 h) and a statistically significant increase of HepG2 cells arrested in G2/M phase. In addition, it altered mitochondrial membrane potential and induced chromosomal DNA fragmentation (24 h). In HepaRG cells, PhSeZnCl was able to determine a cell cycle-independent induction of apoptosis. Particularly, 50 µg/mL induced mitochondrial membrane depolarization after 24 h and apoptosis after 4 h treatment. Futhermore, all PhSeZnCl concentrations tested determined a significant increase of apoptotic cells after 24 h. Apoptosis was also highlighted by the detection of active Caspase-3 by Western Blot analysis after 24 h exposure. In conclusion, this first toxicological assessment provides new insights into the biological activity of PhSeZnCl in preclinical hepatic models that will be useful in future safety assessment investigation of this compound as a potential pharmaceutical. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-022-00148-y.

Genotoxicity assessment of 1,4-anhydro-4-seleno-D-talitol (SeTal) in human liver HepG2 and HepaRG cells.

1,4-Anhydro-4-seleno-D-talitol (SeTal) is a highly water-soluble selenosugar with interesting antioxidant and skin-tissue-repair properties; it is highly stable in simulated gastric and gastrointestinal fluids and is a potential pharmaceutical ingredient that may be administered orally. Hepatic toxicity is often a major problem with novel drugs and can result in drug withdrawal from the market. Predicting hepatotoxicity is therefore essential to minimize late failure in the drug-discovery process. Herein, we report in vitro studies to evaluate the cytotoxic and genotoxic potential of SeTal in HepG2 and hepatocyte-like differentiated HepaRG cells. Except for extremely high concentrations (10 mM, 68 h-treatment in HepG2), SeTal did not affect the viability of each cell type. While the highest examined concentrations (0.75 and 1 mM in HepG2; 1 mM in HepaRG) were observed to induce primary DNA damage, SeTal did not exhibit clastogenic or aneugenic activity toward either HepG2 or HepaRG cells. Moreover, no significant cytostasis variations were observed in any experiment. The clearly negative results observed in the CBMN test suggest that SeTal might be used as a potential active pharmaceutical ingredient. The present study will be useful for the selection of non-toxic concentrations of SeTal in future investigations.

Cytogenetic Effects in Children Exposed to Air Pollutants: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to assess the association between exposure to ambient air pollutants and micronuclei (MN) frequency in children. This work was performed according to the Cochrane Collaboration and the PRISMA guidelines and recommendations. Articles published before November 2021 were identified by an advanced search on PubMed/MEDLINE, Scopus and Web of Science databases. A critical appraisal using a specific tool was conducted to assess the quality of each included study. All analyses were carried out by using the Review Manager (RevMan) 5.4 software (The Cochrane Collaboration, London, UK). One hundred and forty-five references were firstly identified, and, at the end of selection process, 13 studies met the inclusion criteria. Six studies carried out a direct evaluation through the use of air samplers, whereas the other ones accessed environmental databases (n = 2) or used other tools (n = 3). In two cases, exposure was not directly investigated, with children sampled in two different areas with well-known different levels of pollution. The overall effect size (ES) was 1.57 ((95% CI = 1.39; 1.78), p-value < 0.00001) (total evaluated subjects: 4162), which highlighted a statistically significant association between outdoor air pollution and MN frequency in children. As a high MN frequency has been associated with a number of pathological states and a higher risk of developing chronic degenerative diseases, our results should be taken into consideration by policy makers to design and implement interventions aimed at reducing the introduction of pollutants in the atmosphere as well as at minimizing the exposure extent, particularly in children.

Cytotoxicity and Genotoxicity of Senecio vulgaris L. Extracts: An In Vitro Assessment in HepG2 Liver Cells.

Senecio vulgaris L. is a herbaceous species found worldwide. The demonstrated occurrence of pyrrolizidine alkaloids in this species and its ability to invade a great variety of habitats result in a serious risk of contamination of plant material batches addressed to the herbal teas market; this presents a potential health risk for consumers. In light of the above, this work aimed to assess the cytotoxic and genotoxic activity of S. vulgaris extracts in HepG2 cells. Dried plants were ground and extracted using two different methods, namely an organic solvent-based procedure (using methanol and chloroform), and an environmentally friendly extraction procedure (i.e., aqueous extraction), which mimicked the domestic preparation of herbal teas (5, 15, and 30 min of infusion). Extracts were then tested in HepG2 cells for their cytotoxic and genotoxic potentialities. Results were almost superimposable in both extracts, showing a slight loss in cell viability at the highest concentration tested, and a marked dose-dependent genotoxicity exerted by non-cytotoxic concentrations. It was found that the genotoxic effect is even more pronounced in aqueous extracts, which induced primary DNA damage after five minutes of infusion even at the lowest concentration tested. Given the broad intake of herbal infusions worldwide, this experimental approach might be proposed as a screening tool in the analysis of plant material lots addressed to the herbal infusion market.

Assessment of primary, oxidative and excision repaired DNA damage in hospital personnel handling antineoplastic drugs.

The International Agency for Research on Cancer has classified several antineoplastic drugs in Group 1 (human carcinogens), among which chlorambucil, cyclophosphamide (CP) and tamoxifen, Group 2A (probable human carcinogens), among which cisplatin, etoposide, N-ethyl- and N-methyl-N-nitrosourea, and Group 2B (possible human carcinogens), among which bleomycins, merphalan and mitomycin C. The widespread use of these mutagenic/carcinogenic drugs in the treatment of cancer has led to anxiety about possible genotoxic hazards to medical personnel handling these drugs. The aim of the present study was to evaluate work environment contamination by antineoplastic drugs in a hospital in Central Italy and to assess the genotoxic risks associated with antineoplastic drug handling. The study group comprised 52 exposed subjects and 52 controls. Environmental contamination was assessed by taking wipe samples from different surfaces in preparation and administration rooms and nonwoven swabs were used as pads for the surrogate evaluation of dermal exposure, 5-fluorouracil and cytarabine were chosen as markers of exposure to antineoplastic drugs in the working environment. The actual exposure to antineoplastic drugs was evaluated by determining the urinary excretion of CP. The extent of primary, oxidative and excision repaired DNA damage was measured in peripheral blood leukocytes with the alkaline comet assay. To evaluate the role, if any, of genetic variants in the extent of genotoxic effects related to antineoplastic drug occupational exposure, the study subjects were genotyped for GSTM1, GSTT1, GSTP1 and TP53 polymorphisms. Primary DNA damage significantly increased in leukocytes of exposed nurses compared to controls. The use of personal protective equipment (i.e. gloves and/mask) was associated with a decrease in the extent of primary DNA damage.

Lifestyle, WCRF/AICR Recommendations, and Esophageal Adenocarcinoma Risk: A Systematic Review of the Literature.

One of the most notable changes in the epidemiology of esophageal cancer (EC) is the rising incidence and prevalence of esophageal adenocarcinoma (EAC) in developed countries. The aim of this systematic review was to collect and summarize all the available evidence regarding lifestyle, diet, and EAC risk. We searched the PubMed and Scopus databases in January 2021 for studies providing information about lifestyle, diet, WCRF/AICR recommendations, and EAC risk; published in English; without a time filter. The Newcastle-Ottawa Scale was used to assess risk of bias. The results are stratified by risk factor. A total of 106 publications were included. Half of the case-control studies were judged as high quality, whilst practically all cohort studies were judged as high quality. Body mass index and waist circumference were associated with increased EAC risk. Physical activity did not appear to have a significant direct role in EAC risk. A diet rich in fruit, vegetables, and whole grains appeared to be more protective than a Western diet. Alcohol does not seem to be related to EAC, whereas smokers, particularly heavy smokers, have an increased risk of EAC. Prevention remains the best option to avert EAC. Comprehensible and easy to follow recommendations should be provided to all subjects. Protocol ID number: CRD-42021228762, no funds received.

Dietary Fiber Intake and Risk of Pancreatic Cancer: Systematic Review and Meta-Analysis of Observational Studies.

The burden of pancreatic cancer varies greatly across countries, with the number of deaths, incident cases, and disability-adjusted life years more than doubling in recent years, and with high-income countries having the highest incidence and mortality rates. We conducted this systematic review with meta-analysis with the goal of summarizing the current evidence on dietary fiber intake and its role in reducing the risk of pancreatic cancer, given the importance of identifying risk factors. This systematic review followed the guidelines of the Cochrane Collaboration and the Meta-analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The structured literature search was conducted on PubMed/Medline and Scopus, combining free text words and medical subject headings. Our review contained 18 records at the end of the process. Our results show that dietary fiber intake reduces the risk of pancreatic cancer. When the analysis was differentiated according to the type of fiber considered, sub-grouped by gender (reduction of around 60% among women), and when case-control studies were conducted, the strength of the association increased. Clinicians and policymakers should improve interventions to raise the population's awareness regarding the consumption of high-fiber diets, both in practice and in terms of public health policy.

Association between Dietary Fibre Intake and Colorectal Adenoma: A Systematic Review and Meta-Analysis.

PubMed/Medline, Excerpta Medica dataBASE (EMBASE) and Scopus were searched in January 2021 in order to retrieve evidence assessing the association between dietary fibre intake and the risk of colorectal adenoma in adults. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for the reporting of results. Only primary observational studies were included. Publication bias was estimated through the Egger's test and the visual inspection of the funnel plot. Heterogeneity between studies was calculated with I2 statistics. The search strategy identified 683 papers, 21 of which were included in our meta-analysis. Having evaluated a total of 157,725 subjects, the results suggest a protective effect of dietary fibre intake against colorectal adenoma. Effect Size (ES) was [0.71 (95% CI = 0.68-0.75), p = 0.000)]. Moderate statistical heterogeneity (Chi2 = 61.68, df = 23, I2 = 62.71%, p = 0.000) was found. Findings show a statistically significant (p = 0.000) and robust association between a higher intake of dietary fibre and a lower risk of colorectal adenoma, considering both the prevalent and incident risk. Moreover, the meta-regression analysis showed a borderline significant negative linear correlation between the amount of dietary fibre intake and colorectal adenoma. Lastly, we performed a subgroup analysis by sex, showing a higher protective effect for men.

Pro-Apoptotic Activity of Artichoke Leaf Extracts in Human HT-29 and RKO Colon Cancer Cells.

(1) Background: Cynara cardunculus L. subsp. scolymus (L.) Hegi, popularly known as artichoke, is an herbaceous plant belonging to the Asteraceae family. Artichoke leaf extracts (ALEs) have been widely used in traditional medicine because of their hepatoprotective, cholagogic, hypoglycaemic, hypolipemic and antibacterial properties. ALEs are also recognized for their antioxidative and anti-inflammatory activities. In this study, we evaluated the cytotoxic, genotoxic, and apoptotic activities, as well as effect on cell growth of ALEs on human colon cancer HT-29 and RKO cells. HT-29 and RKO cells exhibit a different p53 status: RKO cells express the wild-type protein, whereas HT-29 cells express a p53-R273H contact mutant. (2) Methods: Four different ALEs were obtained by sequential extraction of dried artichoke leaves; ALEs were characterized for their content in chlorogenic acid, cynaropicrin, and caffeoylquinic acids. HT-29 and RKO cells were used for in vitro testing (i.e., cytotoxicity and genotoxicity assessment, cell cycle analysis, apoptosis induction). (3) Results: Two out of the four tested ALEs showed marked effects on cell vitality toward HT-29 and RKO tumour cells. The effect was accompanied by a genotoxic activity exerted at a non-cytotoxic concentrations, by a significant perturbation of cell cycle (i.e., with increase of cells in the sub-G1 phase), and by the induction of apoptosis. (4) Conclusions: ALEs rich in cynaropicrin, caffeoylquinic acids, and chlorogenic acid showed to be capable of affecting HT-29 and RKO colon cancer cells by inducing favourable biological effects: cell cycle perturbation, activation of mitochondrial dependent pathway of apoptosis, and the induction of genotoxic effects probably mediated by the induction of apoptosis. Taken together, these results weigh in favour of a potential cancer chemotherapeutic activity of ALEs.

Red and Processed Meat Consumption and Risk of Depression: A Systematic Review and Meta-Analysis.

Depression is one of the leading causes of disability worldwide, with more than 264 million people affected. On average, depression first appears during the late teens to mid-20s as result of a complex interaction of social, psychological and biological factors. The aim of this systematic review with meta-analysis is to assess the association between red and processed meat intake and depression (both incident and prevalent). This systematic review was conducted according to the methods recommended by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant papers published through March 2020 were identified by searching the electronic databases MEDLINE, Embase and Scopus. All analyses were conducted using ProMeta3 software. A critical appraisal was conducted. Finally, 17 studies met the inclusion criteria. The overall effect size (ES) of depression for red and processed meat intake was 1.08 [(95% CI = 1.04; 1.12), p-value < 0.001], based on 241,738 participants. The results from our meta-analysis showed a significant association between red and processed meat intake and risk of depression. The presented synthesis will be useful for health professionals and policy makers to better consider the effect of diet on mental health status.

Are the Italian Children Exposed to Advertisements of Nutritionally Appropriate Foods?

Unhealthy eating habits are one of the main risk factors for overweight/obesity, and food marketing plays a major role in their development. The aim of this study was to monitor the amount and the characteristics of food marketing directed to Italian children broadcasted on television (TV). The WHO tool to assess food and beverage multimedia marketing aimed at children was used to analyze TV recordings. Type of product branded, viewing time, channel's target, and broadcasting company were the exposure variables analyzed. The power of persuasive techniques was also assessed. Food products were categorized as either core or non-core products on the basis of their nutritional profile. A total of 320 h of TV broadcasting was analyzed, including 51.7 h of commercials. Food and beverages were the second most frequently advertised products, with an average of 6 food advertisements per hour during peak viewing time. A total of 23.8% of food advertisements were recorded during the time slot of 3:00 p.m. Considering food and beverage commercials, "humor" was the most frequently used primary persuasive technique, while the "image of the product/packaging" was the most commonly used secondary persuasive technique. Products specifically targeted to children were 94.3% non-core. Our findings indicate that core foods are highly underrepresented in TV commercials, especially during children TV programs and peak viewing time.

B-Comet Assay (Comet Assay on Buccal Cells) for the Evaluation of Primary DNA Damage in Human Biomonitoring Studies.

Many subjects perceive venous blood collection as too invasive, and thus moving to better-accepted procedures for leukocytes collection might be crucial in human biomonitoring studies (e.g., biomonitoring of occupational or residential exposure to genotoxins) management. In this context, primary DNA damage was assessed in buccal lymphocytes (BLs), fresh whole venous, and capillary blood leukocytes, and compared with that in peripheral blood lymphocytes (PBLs)-the most frequently used cells-in 15 young subjects. Mouthwashes were collected after the volunteers rinsed their mouths with normal saline, and BLs were isolated by density gradient centrifugation. Blood samples were collected by venipuncture or by lancet. Anthropometric and lifestyle information was obtained by the administration of a structured questionnaire. As shown in the Bland-Altman plots, the level of agreement between BLs and PBLs lied within the accepted range, we thus enrolled a wider population (n = 54) to assess baseline DNA damage in BLs. In these cells, mean values of tail length (µm), tail intensity (%), and tail moment were 25.7 ± 0.9, 6.7 ± 0.4 and 1.0 ± 0.1, respectively. No significant association was observed between sex and smoking habit with any of the DNA damage parameters. Conversely, underweight subjects displayed significantly higher genomic instability compared with normal weight group (p < 0.05). In conclusion, we successfully managed to set up and update a non-invasive and well-accepted procedure for the isolation of BLs from saliva that could be useful in upcoming biomonitoring studies.

Extent of Primary DNA Damage Measured by the Comet Assay in Health Professionals Exposed to Antineoplastic Drugs: A Systematic Review and Meta-Analysis.

BACKGROUND: Antineoplastic drugs (ANDs) are a broad group of chemicals showing, at the same time, carcinogenic effects. The potential, albeit true, risk of side effects cannot be accepted, especially if resulting from occupational exposure. The aim of this study was to evaluate the association between occupational exposure to ANDs and the extent of primary DNA damage in health professionals. METHODS: A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/Medline, Web of Science, and Scopus were used to perform the literature search. The databases were examined in July 2019. Sub-group, moderator, and cumulative analyses were conducted. The trim and fill method was used in the case of potential publication bias. RESULTS: Twenty studies were included in the qualitative analysis, and 19 in quantitative evaluation. The pooled effect size was 1.27 [(95% confidence interval (CI) = 0.66-1.88), p = 0.000] based on 1569 subjects. The moderator analysis by duration of exposure showed a positive association between duration of exposure and primary DNA damage. CONCLUSIONS: This systematic review clearly shows a significant association between occupational exposure to ANDs and the extent of primary DNA damage in health professionals. Considering these results, health professionals should be warned against this potential occupational risk.