Mutagen sensitivity in peripheral lymphocytes as a risk indicator

A total of 266 individuals were selected to represent the normal distribution of age, sex, and blood pressure in the general population of Dalby, Sweden. A method designed to estimate an individual's sensitivity to mutagenic exposures has been established and is based on in vitro N-acetoxy-2-acetylaminofluorene (NA-AAF) stimulation of unscheduled DNA synthesis (UDS) in resting peripheral lymphocytes. High levels of NA-AAF-induced UDS, or high mutagen sensitivity, correlated to old age and to high blood pressure. The general health status was described in relation to the estimated mutagen sensitivity by collecting, from the national health insurance records, information regarding all disease episodes during a five-year period. It was found that the incidence of cardiovascular, infectious, and malignant diseases was considerably higher among those individuals assigned high mutagen risk by the NA-AAF-induced UDS method. These data were taken as evidence in support of the hypothesis that lymphocyte sensitivity to the induction of DNA damage by NA-AAF indicates the relative risk of individuals' developing the major diseases important in general health care.     

Hypertension, age, and smoking related to genotoxic sensitivity in human lymphocytes: a population study

The levels of N-acetoxy-2-acetylaminofluorene (NA-AAF)-induced unscheduled DNA synthesis (UDS) were determined in resting mononuclear leukocytes from males in a geographically defined population. The mutagen sensitivity, as determined by the NA-AAF method, was associated with the risk indicators of cerebrocardiovascular disease (CCVD) rather than with CCVD itself. Thus, high blood pressure, age, and smoking--some of the most important risk indicators of CCVD--seem to be conditions which predispose an individual's mononuclear blood cells to increased likelihood of accumulating DNA damage. Hypertensives evidenced higher values of NA-AAF-induced UDS than did nonhypertensive controls, even though the former were treated in accordance with internationally accepted norms. We have previously shown that hypertensives with normalized blood pressure did not differ from controls, when assessed by the NA-AAF method. In the present study, the hypertensives' blood pressure values were 19/12 mm Hg higher than those of the controls, indicating a need for more intensive treatment. Borderline hypertensives did not differ from their controls when assessed by the NA-AAF method, even though their blood pressure values were 19/9 mm Hg higher than those of their controls. This indicates that the group of borderline hypertensives may be heterogeneous, and that some of the patients may be suffering from a condition different from that in those with established hypertension.     

Morinda Citrifolia (Noni) Reduces Cancer Risk in Current Smokers by Decreasing Aromatic DNA Adducts

Quantitative determination of aromatic DNA adducts in peripheral blood lymphocytes (PBLs) of current smokers is an useful surrogate biomarker for the evaluation of environmental carcinogen exposure or chemopreventive intervention. In this study, we examined the impact of Tahitian Noni Juice (TNJ) on the aromatic DNA adducts of PBLs, before and after a 1-mo intervention, using ³²P postlabeling assay. Of 283 enrolled, 203 smokers completed the trial. Aromatic DNA adducts levels in all participants were significantly reduced by 44.9% (P < 0.001) after drinking 1 to 4 oz of TNJ for 1 mo. Dose-dependent analyses of aromatic DNA adduct levels showed reductions of 49.7% (P < 0.001) in the 1-oz TNJ group and 37.6% (P < 0.001) in the 4-oz TNJ group. Gender-specific analyses resulted in no significant differences in the 4-oz TNJ groups. Interestingly, the 1-oz TNJ group showed a reduction of 43.1% (P < 0.001) in females compared with 56.1% (P < 0.001) in males. The results suggest that drinking 1 to 4 oz of TNJ daily may reduce the cancer risk in heavy cigarette smokers by blocking carcinogen-DNA binding or excising DNA adducts from genomic DNA.     

450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy

Background: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear.Objective: We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy.Methods: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K).Results: We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 × 10^–7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke.Conclusions: We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.     

香烟烟雾冷凝物诱导体外培养细胞程序外DNA合成的试验研究

采用程序外ＤＮＡ合成试验方法检测香烟冷凝物对体外培养的人表皮细胞和人全血淋巴细胞ＤＮＡ的损伤作用。结果表明，香烟冷凝物能引起培养的表皮细胞和淋巴细胞的ＤＮＡ损伤；在一定的作用物剂量范围内表现出剂量效应关系。由于在细胞培养环境中未加Ｓ９组分活化酶，提示冷凝物中含有不需代谢活化就能直接导致ＤＮＡ损伤的有害物质。     

利用生物发光法测定人群外周淋巴细胞DNA加合物水平

目的：利用生物发光法测定人群外周淋巴细胞DNA加合物水平,并分析其影响因素,为进一步探讨水污染与人群DNA加合物水平之间的关系奠定基础,方法：采用随机整群抽样方法,抽取234例健康人群,测定其外周淋巴细胞DNA加合物水平,并对年龄,吸烟,饮食习惯等进行分析。结果：健康人群中男性DNA加合物水平略高于女性,但二之间差异无显意义;人群DNA加合物与年龄,吸烟,饮茶,饮食习惯和饮酒等因素均有显相关性,其中年龄,吸烟与DNA加合物的相关性最为明显;随着年龄的增加,DNA加合物水平上升;吸烟越多;DNA加合物水平越高,结论：人群DNA加合物水平影响因素很多,其在人体生物监测,肿瘤形成风险评估中的应用,还有待进一步的研究。     

Obesity with a body mass index under 30 does not significantly impair the immune response in young adults

Obesity accompanies various metabolic and immunologic changes. Evidence from epidemiological, animal, and human studies has linked obesity to impaired immunity. However, human studies that have investigated the immunocompetence of the obese are still limited. We studied the immune and inflammatory responses of obese (body mass index [BMI], 28.3 ± 0.5 kg/m²; n = 30) and normal-weight (BMI, 21.2 ± 0.3 kg/m²; n = 15) young adults to test the hypothesis that obesity is associated with an impaired immune function and dysregulated inflammatory response. Serum levels of adipokines and subpopulations of immune cells were examined. In vitro proliferative response of whole blood lymphocytes, the production of inflammatory cytokines (interleukin [IL] 1β, IL-6, and tumor necrosis factor α) and T helper 1/T helper 2 cytokines (IL-2, interferon γ, IL-4, and IL-10) were determined. Serum leptin levels were significantly higher (P < .001) and CD8⁺ T-cell subpopulation was significantly lower (P = .044) in the obese than normal-weight subjects. There was no difference in the proliferative response of whole-blood lymphocytes to T-cell mitogens between 2 groups. Phytohemagglutinin-stimulated peripheral blood mononuclear cells from the obese group produced significantly higher levels of IL-2 (P = .002) and tended to produce higher levels of IL-4 (P = .053) than those from the normal-weight group. No significant differences in the production of inflammatory cytokines by either whole-blood lymphocytes or peripheral blood mononuclear cells stimulated with lipopolysaccharide were observed between the obese and normal-weight subjects. These results suggest that obesity with a BMI less than 30 does not significantly impair immune function in young adults. However, further research is needed to investigate the clinical significance of a lower CD8⁺ T-cell population associated with obesity.     

Differential DNA Methylation in Umbilical Cord Blood of Infants Exposed to Low Levels of Arsenic in Utero

Background: There is increasing epidemiologic evidence that arsenic exposure in utero, even at low levels found throughout much of the world, is associated with adverse reproductive outcomes and may contribute to long-term health effects. Animal models, in vitro studies, and human cancer data suggest that arsenic may induce epigenetic alterations, specifically by altering patterns of DNA methylation.Objectives: In this study we aimed to identify differences in DNA methylation in cord blood samples of infants with in utero, low-level arsenic exposure.Methods: DNA methylation of cord-blood derived DNA from 134 infants involved in a prospective birth cohort in New Hampshire was profiled using the Illumina Infinium Methylation450K array. In utero arsenic exposure was estimated using maternal urine samples collected at 24–28 weeks gestation. We used a novel cell mixture deconvolution methodology for examining the association between inferred white blood cell mixtures in infant cord blood and in utero arsenic exposure; we also examined the association between methylation at individual CpG loci and arsenic exposure levels.Results: We found an association between urinary inorganic arsenic concentration and the estimated proportion of CD8⁺ T lymphocytes (1.18; 95% CI: 0.12, 2.23). Among the top 100 CpG loci with the lowest p-values based on their association with urinary arsenic levels, there was a statistically significant enrichment of these loci in CpG islands (p = 0.009). Of those in CpG islands (n = 44), most (75%) exhibited higher methylation levels in the highest exposed group compared with the lowest exposed group. Also, several CpG loci exhibited a linear dose-dependent relationship between methylation and arsenic exposure.Conclusions: Our findings suggest that in utero exposure to low levels of arsenic may affect the epigenome. Long-term follow-up is planned to determine whether the observed changes are associated with health outcomes.     

Bovine lactoferrin supplementation supports immune and antioxidant status in healthy human males

Dietary supplements of bovine lactoferrin are purported in consumer literature to enhance and support the immune system response through their antioxidant, antibacterial, and antiviral properties. Our aim was to investigate more fully the potential immune modulating properties and antioxidant activity of an oral supplementation of bovine lactoferrin in humans. Using an intraindividual repeated measure design, 8 healthy males aged 30 to 55 years, self-administered daily for 21 days, one capsule of placebo for 7 days, followed by 100 mg of lactoferrin for 7 days, followed by 200 mg of lactoferrin for 7 days. Peripheral blood lymphocyte subset counts, T-cell activation, natural killer (NK) cell cytotoxicity, serum cytokine levels (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, interleukin [IL]-2, IL-4, IL-6, and IL-10), and serum hydrophilic, lipophilic, and total antioxidant capacity were repeatedly measured before and after each progressive supplementation. Statistically significant increases were found between presupplementation levels and levels after 200 mg of supplementation in total T-cell activation (as measure by CD3⁺) (P < .001), helper T-cell activation (as measure by CD4⁺) (P < .001), cytotoxic T-cell activation (as measured by CD8⁺) (P < .001), and hydrophilic antioxidant capacity (P < .05). No significant changes were seen in the other parameters measured. These results support the proposal that oral supplements of bovine lactoferrin may be a useful adjunct toward modulation of immune activity, in particular T-cell activation and antioxidant status.     

Decreasing urinary PAH metabolites and 7-methylguanine after smoking cessation

Objective: Humans are exposed to various carcinogens by smoking. Urinary metabolites of polycyclic aromatic hydrocarbons (PAH), one of the major carcinogens in cigarette smoke, were measured as the environmental carcinogen exposure marker for humans. We evaluated urinary exposure markers for smoking cessation. Method: In this study, we measured cigarette smoke exposure markers, such as urinary cotinine, PAH exposure markers, such as urinary 1-hydroxypyrene (1-OHP), 2-naphthol (2-NP) and 1-naphthol (1-NP), as well as a methylating chemical exposure marker, 7-methylguanine (7-MeG). The before smoking cessation levels of these markers, and the after smoking cessation levels were then compared. Eighteen subjects participated in this smoking cessation program. Results: Levels of all of four markers were found to have decreased by 19–54% after smoking cessation. Urinary cotinine, 1-OHP, 2-NP and 7-MeG levels were found to have significantly decreased after smoking cessation. There were positive correlations between cotinine and three urinary PAH markers and between 1-OHP, 2-NP and 7-MeG. Conclusion: PAH metabolites were better biomarkers of smoking cessation than 7-MeG. Analyzing urinary metabolites or urinary DNA adducts is suitable for epidemiological studies.     

Monitoring of occupational exposure to polycyclic aromatic hydrocarbons in a carbon-electrode manufacturing plant

An investigation is presented of occupational exposure to polycyclic aromatic hydrocarbons (PAH) in a carbon-electrode manufacturing plant, as assessed by three monitoring methods, viz. environmental monitoring of the external dose by analysis of personal air samples, biological monitoring of the internal dose by analysis of urinary 1-hydroxypyrene (1-OHpyrene), and biological effect monitoring by dosimetry of PAH-DNA adducts in blood lymphocytes. On the basis of job conditions, workers at the plant were divided into three groups with presumed low, intermediate and high exposure to air-borne PAH, respectively. All air samples showed levels of total PAH below the current MAC-value in the Netherlands, which is 200 μg/m³, whereas the benzo[a]pyrene level was occasionally higher than the recommended concentration of 2 μg/m³. The values of 1-OHpyrene in urine from the intermediate and high exposure groups were significantly higher than those of the low exposure group, namely 3.6- and 8.2-fold, respectively. Clear external and internal exposure was thus demonstrated for workers of the high and intermediate exposure groups, but this did not result in a measurable effect at the DNA level in blood lymphocytes. Tobacco smoking, on the other hand, caused a significant increase of the levels of PAH-DNA adducts but did not affect 1-OHpyrene values. These data suggest that smoking is a more important risk factor for adverse health effects, i.e. cancer, than occupational exposure to PAH in this plant.     

Study of Secondhand Smoke Levels Pre and Post Implementation of the Comprehensive Smoking Ban in Mumbai

Objectives:

This research was undertaken with the aim of assessing the indoor air quality in popular hospitality venues, as also to evaluate the effectiveness of the nationwide comprehensive public smoking ban. The analysis was split into two halves – baseline study taken up prior to implementation of the said ban on 2^nd October 2008, and the follow-up study after it came into effect.

Materials and Methods:

Twenty-five venues including five restaurants, fourteen resto-bars, two hookah (smoking water-pipe) cafes and four pubs were selected using a mix of random, convenience and purposeful sampling. Particulate matter (PM_2.5) measurements at these venues were made using TSI SidePak AM510 Personal Aerosol Monitor.

Results:

The average PM_2.5 level in venues where smoking was permitted prior to implementation of ban was found to be 669.95 μg/m³ in the baseline study. Post ban, the average PM_2.5 level in same test venues reduced to 240.8 μg/m³. The hookah cafes were an exception as the average PM_2.5 levels exceeded the permissible limits before as well as post ban.

Conclusion:

The baseline study showed that the hospitality venues had hazardous levels of PM_2.5 particles arising from second-hand smoke prior to smoking ban. These decreased by a maximum of 64% after the law took effect. A substantial improvement in air quality at these venues post implementation of the smoking ban indicated the effectiveness of the law.     

Effect of Probiotic Supplement on Cytokine Levels in HIV-Infected Individuals: A Preliminary Study

Inflammation persists in patients infected with HIV. Reduction of inflammatory cytokines and microbial translocation might be one way that this could be managed. Purpose: The anti-inflammatory properties of certain probiotic strains prompted us to investigate whether a probiotic could reduce the inflammatory index of HIV-infected patients. Methods: The study involved 30 HIV+ males on antiretroviral therapy, who were given one bottle of fermented milk Yakult Light^® containing Lactobacillus casei Shirota (LcS) twice a day for four weeks. Results: The probiotic LcS was associated with an increase of T lymphocytes and a significant increase of CD56+ cells (p = 0.04). There was also a significant decrease of mRNA levels of TGFβ, IL-10 and IL-12 (p < 0.001) and IL-1β expression (p < 0.001) and an increase of serum IL-23 (p = 0.03). In addition, decreased inflammation and cardiovascular risk were observed, as shown by a reduction of cystatin C (p < 0.001). Conclusions: These data provide preliminary evidence that probiotic supplementation may modulate certain immunological parameters and some of the cytokines that were analyzed. Thus, we propose that LcS may be an inexpensive and practical strategy to support the immune function of HIV+ patients.     

In vitro induction of unscheduled DNA synthesis by genotoxic carcinogens in the hepatocytes of the oyster toadfish (Opsanus tau)

The possibility that the measurement of unscheduled DNA synthesis (UDS) can be used to investigate the genotoxic effects of mutagenic carcinogens in a marine fish was examined. Primary cultures of hepatocytes from the oyster toadfish (Opsanus tau) were exposed to two direct-acting and two activation-dependent genotoxic carcinogens and incorporation of³H-thymidine (3HT) by the nuclei of non-replicating cells was assessed autoradiographically. 4-Nitroquinoline-1-oxide (4NQO) induced significant increases in silver grains/nucleus at 10^–9M, 10^–6M and 10^–5M concentrations. Ethyl methanesulfonate (EMS) induced significant UDS at 10^–2M and 10^–1M concentrations. Benzo(a)pyrene (BAP) induced significant UDS at 10^–6, 10^–5M and 10^–4M concentrations. 2-Aminoanthracene (2AA) induced significant UDS only at the 10^–5M concentration. The results suggest that toadfish hepatocytes exhibit a generally lower and a more variable response than do rat hepatocytes in similar assays. If the potency of a chemical in the UDS assay is inversely related to the concentration at which the maximum UDS response for a chemical is obtained, the potency ranking for the chemicals tested in toadfish hepatocytes was BAP > 4NQ0=2AA > EMS. The relative potencies of the direct acting test chemicals were the same as reported for rat hepatocytes, whereas the relative potency of the activation-dependent test chemicals (BAP and 2AA) were different than reported for the rat. The results suggest that the activation of BAP and 2AA are different in intact toadfish and rat hepatocytes. The possible applications of UDS assay procedures in aquatic toxicology are discussed.Primary support for this research was provided by US Environmental Protection Agency (EPA) Grant 808251-01. This paper does not necessarily reflect EPA policy. Additional support was provided by the Slocum-Lunz Foundation.     

Detection of DNA single-strand breaks in lymphocytes of smokers

Summary In a controlled study, ten male volunteers (five smokers and five nonsmokers) were subjected to different smoking conditions and compared to five non-smokers, not exposed to cigarette smoke. During the 4 days of the study, nonsmoking periods were strictly controlled. On the first day the ten subjects were sham exposed. On the second day the five smokers smoked 24 cigarettes in 8 h, while the five nonsmokers were exposed to the environmental tobacco smoke. After another day of sham exposure the smoke exposure was repeated under the same conditions. Blood was drawn before and after exposure and DNA single-strand breaks (SSBs) were analyzed in lymphocytes immediately (1 h) after isolation of cells and after 4 h incubation at 37°C, using a modified assay based on the nick translation reaction. Base levels of unscheduled DNA synthesis (UDS) and UDS levels were determined after 1 h incubation with methyl methanesulfonate. Duplicate analysis using the same method was performed in a second laboratory after transportation of blood samples at 0°C on a train from Munich to Hamburg. Tobacco smoke exposure of the subjects increased COHb and plasma cotinine levels. SSBs could be detected in all probands with some inter-individual day-to-day and morning-to-evening variations. In four of five active smokers, SSB increases were found after smoking. In nonsmokers exposed to tobacco smoke no exposure-related variation in SSB levels could be detected. In lymphocytes which were incubated in culture medium (DME/H) for 4 h at 37°C, SSBs correlated significantly with the SSBs of fresh (NT1) samples but the SSB level was lower in almost all cases and the effect of smoking was not as pronounced as in the NT1 samples. Larger interindividual variations and higher values in general were detected after 8–9h of transportation. Therefore, we recommend immediate determination of SSBs as soon as possible after blood sampling. We conclude that the modified nick translation assay is sensitive enough to detect SSBs caused by an in vivo genotoxic exposure when possible interindividual differences are considered in the study design and could therefore be used in biological monitoring of exposures at the workplace.     

Oxidative DNA damage and inflammatory responses in cultured human cells and in humans exposed to traffic-related particles

Particulate pollution is a major public health concern because epidemiological studies have demonstrated that exposure to particles is associated with respiratory diseases and lung cancer. Diesel exhaust particles (DEP), which is classified as a human carcinogen (IARC, 2012), are considered a major contributor to traffic-related particulate matter (PM) in urban areas. DEP consists of various compounds, including PAHs and metals which are the principal components that contribute to the toxicity of PM. The present study aimed to investigate effects of PM on induction of oxidative DNA damage and inflammation by using lymphocytes in vitro and in human exposed to PM in the environment. Human lymphoblasts (RPMI 1788) were treated with DEP (SRM 2975) at various concentrations (25–100 μg/ml) to compare the extent of responses with alveolar epithelial cells (A549). ROS generation was determined in each cell cycle phase of DEP-treated cells in order to investigate the influence of the cell cycle stage on induction of oxidative stress. The oxidative DNA damage was determined by measurement of 8-hydroxy-deoxyguanosine (8-OHdG) whereas the inflammatory responses were determined by mRNA expression of interleukin-6 and -8 (IL-6 and IL-8), Clara cell protein (CC16), and lung surfactant protein-A (SP-A). The results showed that RPMI 1788 and A549 cells had a similar pattern of dose-dependent responses to DEP in terms of particle uptake, ROS generation with highest level found in G2/M phase, 8-OHdG formation, and induction of IL-6 and IL-8 expression. The human study was conducted in 51 healthy subjects residing in traffic-congested areas. The effects of exposure to PM_2.5 and particle-bound PAHs and toxic metals on the levels of 8-OHdG in lymphocyte DNA, IL-8 expression in lymphocytes, and serum CC16 were evaluated. 8-OHdG levels correlated with the exposure levels of PM_2.5 (P < 0.01) and PAHs (P < 0.05), but this was not the case with IL-8. Serum CC16 showed significantly negative correlations with B[a]P equivalent (P < 0.05) levels, but positive correlation with Pb (P < 0.05). In conclusion, a similar pattern of the dose-dependent responses to DEP in the lymphoblasts and lung cells suggests that circulating lymphocytes could be used as a surrogate for assessing PM-induced oxidative DNA damage and inflammatory responses in the lung. Human exposure to PM leads to oxidative DNA damage whereas PM-induced inflammation was not conclusive and should be further investigated.     

Association of total and neutralizing SARS-CoV-2 spike -receptor binding domain antibodies with epidemiological and clinical characteristics after immunization with the 1st and 2nd doses of the BNT162b2 vaccine

BackgroundData regarding the association of antibody levels elicited after immunization with the BNT162b2 mRNA COVID-19 vaccine with epidemiological and clinical parameters are limited.MethodsWe prospectively measured the total (TAbs-RBD) and the neutralizing antibodies (NAbs-RBD) against the receptor binding domain (RBD) of SARS-CoV-2 spike protein in a cohort of 268 Healthcare workers before immunization, 20 days after the 1^st dose and 30 days after the 2^nd dose of the BNT162b2 vaccine. A statistical analysis for possible association of antibodies’ levels with epidemiological and clinical parameters was performed.ResultsThe mean age (±SD) of the participants was 45.45 years (±11.93) (range: 24–70 years) and 211 (79.9%) were females. Statistically significant differences were detected regarding both TAbs-RBD and NAbs-RBD between the first and second doses of the vaccine (P < 0.001). The median (IQR) percentage (%) of NAbs-RBD after the 1^st dose was 51.07% (31.60%) and after the 2^nd dose 95.31% (3.70%) (P < 0.001). The correlation between the TAbs-RBD and NAbs-RBD was after the 1^st dose, Spearman’s, rho: 0.861 (P < 0.001) and after the 2^nd dose rho: 0.989 (P < 0.001). Twenty days after the 1^st dose, 56/264 (21.2%) of the participants had low levels of NAbs-RBD, while one month after the 2^nd dose all of them had protective levels of NAbs-RBD. After the 2^nd vaccine dose, a statistically significant negative association of TAbs-RBD was detected for age (P < 0.001), smoking (P = 0.011), and immunosuppressive medications (P < 0.001), while a positive association was detected for BMI (P = 0.004) and systemic adverse events after immunization (P = 0.001).ConclusionA significant correlation of TAbs-RBD and NAbs-RBD was detected after both vaccine doses. Older age, smoking, and immunosuppressive medications negatively affected the final antibody level after SARS-CoV-2 immunization. Our findings emphasize the significance of the 2^nd vaccine dose especially in the older age groups.     

甲基汞对小鼠淋巴细胞程序外DNA合成的影响

目的　了解甲基汞对小鼠淋巴细胞DNA损伤修复的影响。方法　采用离体程序外DNA合成 (UDS)的方法。结果　在一定剂量范围内 ,甲基汞可使小鼠外周血淋巴细胞和胸腺细胞程序外DNA合成能力增强 ,1 0mmol/L组血淋巴细胞和 5 0mmol/L组胸腺细胞UDS明显高于对照组 (P <0 0 5) ,而低剂量组和高剂量组的UDS均低于对照组。结论　甲基汞对小鼠外周血淋巴细胞和胸腺细胞DNA有损伤作用 ,其程度与甲基汞剂量有关 ,甲基汞具有遗传毒性和免疫毒性。     

Effects of (−)-epigallocatechin gallate (EGCG) on DNA strand breaks as evaluated by single-cell gel electrophoresis (SCG) in human lymphocytes

(−)-Epigallocatechin gallate (EGCG), a catechin polyphenol component, is the main ingredient of green tea extract. Although the anti-carcinogenic and cancer inhibitory effects of EGCG have been widely reported, its genotoxicity is not clear and seldom reported. In this study, we examined the effects of EGCG on DNA strand breaks in the isolated lymphocytes and whole blood lymphocytes obtained from two smoking subjects and a nonsmoking healthy subject using a single cell gel electrophoresis (SCG) assay. The results showed that after 2 hrs of treating the isolated lymphocytes from the smokers, EGCG induced a significant, increase in DNA strand breaks at concentrations from 2.5×10⁻⁵ M to 2.0×10⁻⁴ M, while after 2 hrs of treating the whole blood obtained from the same smokers, EGCG suppressed the DNA strand breaks in the lymphocytes at concentrations of 1.0×10⁻⁴ M and 2.0×10⁻⁴ M. A similar suppressive result was also shown in the whole blood lymphocytes from the nonsmoker at nearly the same concentrations, while at concentrations of 1.0×10⁻³ M or 2.0×10⁻³ M, EGCG induced a significant increase in DNA strand breaks in the whole blood lymphocytes from the nonsmoker. This result suggests that EGCG is not only inhibitory against DNA strand breaks in whole blood, but also genotoxic to the isolated or whole blood lymphocytes at high concentrations. Thus, more research is needed to comprehensively assess the effects of EGCG on genetic materials.     

The Associations Between Smoking Habits and Serum Triglyceride or Hemoglobin A1c Levels Differ According to Visceral Fat Accumulation

Background

Whether smokers and former smokers have worse lipid profiles or glucose levels than non-smokers remains unclear.

Methods

The subjects were 1152 Japanese males aged 42 to 81 years. The subjects were divided according to their smoking habits (nonsmokers, former smokers, and current smokers) and their visceral fat area (VFA) (<100 cm² and ≥100 cm²).

Results

The serum triglyceride (TG) levels of 835 males were assessed. In the VFA ≥100 cm² group, a significantly greater proportion of current smokers (47.3%) exhibited TG levels of ≥150 mg/dL compared with former smokers (36.4%) and non-smokers (18.8%). The difference in TG level distribution between former smokers and non-smokers was also significant. However, among the subjects with VFA of <100 cm², the TG levels of the three smoking habit groups did not differ. The serum hemoglobin A1c (HbA1c) levels of 877 males were also assessed. In the VFA <100 cm² group, significantly higher proportions of current smokers (17.9%) and former smokers (14.9%) demonstrated HbA1c levels of ≥5.6% compared with non-smokers (6.3%). In contrast, in the VFA ≥100 cm² group, significantly fewer former smokers displayed HbA1c levels of ≥5.6% compared with non-smokers and current smokers. Furthermore, the interaction between smoking habits and VFA was associated with the subjects’ TG and HbA1c concentrations, and the associations of TG and HbA1c concentrations and smoking habits varied according to VFA.

Conclusions

Both smoking habits and VFA exhibited associations with TG and HbA1c concentrations. The associations between smoking habits and these parameters differed according to VFA.Key words: smoking habits, visceral fat, interaction, serum triglycerides, hemoglobin A1c