DNA修复抑制状态下苯并(a)芘对人胚肺成纤维细胞的DNA损伤作用

目的研究DNA修复抑制状态下苯并(a)芘[B(a)P]对人胚肺成纤维细胞(HELF)的DNA损伤情况,探讨DNA修复机制在外源性化学致癌物诱导真核细胞DNA损伤中的作用。方法代谢活化条件下,以阿糖胞苷(ara-C,0、100μmol/L)与B(a)P(0、10、20、50μmol/L)按2×4联合染毒2h,通过彗星试验观察不同染毒条件下HELF细胞的DNA损伤情况。同时设阴性对照组(0.1%DMSO)和阳性对照组(10μmol/LK2CrO7)。结果与阴性对照组比较,B(a)P各剂量组的HELF的拖尾率、Olive尾矩随剂量增加而显著升高,差异有统计学意义(P<0.01)。100μmol/Lara-C单独染毒组与阴性对照组比较,拖尾率、Olive尾矩升高,差异有统计学意义(P<0.05,P<0.01)。B(a)P ara-C组与相应剂量的B(a)P组比较,其拖尾率、Olive尾矩升高,差异有统计学意义(P<0.01)。析因分析表明,ara-C与B(a)P诱导HELF的DNA损伤存在交互作用(F=3.219,P=0.024)。ara-C可增强B(a)P对HELF的DNA损伤作用。结论DNA修复抑制在外源性化学致癌物诱导真核细胞DNA损伤中存在重要作用。     

Protection of Vitamin C on Oxidative Damage Caused by Long-Term Excess Iodine Exposure in Wistar Rats

Vitamin C was reported to be able to protect against oxidative damage due to its reducibility. 120 Wistar rats were randomly divided into 4 × 2 groups, including normal iodine (NI), high iodine (HI), low vitamin C (HI + LC), and high vitamin C (HI + HC); potassium iodide (KI) and potassium iodate (KIO₃) were commonly used as additives for iodized salt, so every group was also divided into KI and KIO₃ groups. After 6 months’ feed, the activities of antioxidant enzymes and Lipid Peroxide (MDA) content in serum, liver, kidney, brain, thyroid and lens were determined. In serum, for males, long-term excess iodine intake caused oxidative damage; in the liver, male rats in the HI + LC group had the highest MDA content, which showed that low-dose vitamin C might promote oxidative damage; in kidneys, the MDA content in the HI and HI + LC groups of females was higher; in the brain, high-dose vitamin C could increase the activity of superoxide dismutase (SOD), which was decreased by high iodine intake, and it also decreased MDA content; in the thyroid, for KIO₃, the activity of SOD in the HI group was lower than NI and HI + LC; in the lens, the MDA content in females was lower than males. Long-term excess iodine exposure caused oxidative damage and showed sex difference, and vitamin C had a protective effect on it, especially for high-dose vitamin C.     

血清中维生素C含量与淋巴细胞DNA损伤的相关性探讨

目的：研究维生素C对淋巴细胞损伤的影响。方法：通过检测血清中维生素C的含量和淋巴细胞DNA的损伤程度。选取某皮包厂接触甲苯约100人,采集全血分,离淋巴细胞。DNA损伤程度的分析采用＂彗星＂电泳技术;血清中维生素C的测定采用高效液相色谱法。结果：血清中维生素C的含量大于60μmol/l,与血清中维生素C的含量低于20μmol/l,彗星尾长有显著性差异（p〈0.01）。结论：对于接触甲苯的工人,体内维生素C含量在一定的范围时,可以有效地防止DNA损伤,当体内维生素C含量不足时,体内细胞DNA的损伤增加。对于长期接触低浓度甲苯的工人,每天补充一定的维生素C,可以有效地防止DNA损伤。     

Vitamin C supplementation decreases oxidative DNA damage in mononuclear blood cells of smokers

Summary. Background: Antioxidants, in particular vitamin C, have been suggested to decrease oxidative DNA damage. Such effects have been shown in mononuclear blood cells in the first few hours after ingestion, whereas studies of longer-term effects in well-nourished humans have been mainly negative. Aim: To investigate the antioxidant effect of vitamin C in terms of oxidative DNA damage measured by the comet assay and DNA repair measured by expression of OGG1 mRNA in blood cells of male smokers given 2 × 250 mg vitamin C daily as plain or slow release tablets combined with plain release vitamin E 2 × 91mg, or placebo for 4 wk. Results: This study showed a difference in DNA protective effects between a slow release and a plain release vitamin C formulation. Ingestion of slow release vitamin C formulation was associated with fewer endonuclease III and formamidopyrimidine DNA glycosylase sensitive sites measured by the comet assay in mononuclear blood cells obtained 4 h and 8 h after a single tablet and 4 wk after two tablets a day. Ingestion of the vitamin formulation with plain release only indicated a damage-reducing effect 4 h after intake of a single tablet, and the effect was more apparent on endonuclease III than formamidopyrimidine DNA glycosylase sites. Overall the slow release tablets of vitamin C formulation had a more pronounced and a sustained protective effect on base damage compared with the plain release tablets. Plasma vitamin E was unaltered in the first 12 h after ingestion of a single tablet, suggesting that the antioxidant effect was mediated by vitamin C. Differences in plasma vitamin C levels at steady state could not explain the difference between the two vitamin C formulations, whereas wider amplitudes of plasma vitamin C were seen after ingestion of plain release formulation compared to slow release formulation. Assessment of OGG1 mRNA levels by RT-PCR did not indicate increased expression of this DNA repair gene after 4 wk of vitamin supplementation. Conclusion: This study suggests that long-term vitamin C supplementation at high dose, i. e. 500 mg together with vitamin E in moderate dose, 182mg, decreases the steady-state level of oxidative DNA damage in mononuclear blood cells of smokers.     

双酚A对人胚肝细胞DNA损伤和修复功能的影响

[目的]研究双酚A(BisphenolA,BPA)对人肝L-02细胞DNA损伤修复功能的影响。[方法]分别以1、10、50、100μmol/LBPA和100μmol/LBPA+30μg/LVitC处理L-02细胞,比较处理和未处理的人胚肝L-02细胞在DNA损伤程度、切除修复鼠缺陷交叉互补蛋白1(ERCC1)、尿嘧啶DNA糖基化酶(UDG)、错配修复hMSH2基因(hMSH2)、DNA依赖蛋白激酶复合物(DNA-PKcs)及O6-甲基鸟嘌呤甲基转移酶(MGMT)表达水平的差异。每组细胞数均为1×106个/ml。[结果]BPA处理后,彗星试验显示BPA在低剂量(10μmol/L)时即具有DNA损伤作用(P<0.05),随着剂量增大,DNA损伤效应增加。100μmol/LBPA+30μg/LVitC组DNA损伤效应降低,显示抗氧化剂VitC可减缓BPA所致的DNA损伤效应,氧化损伤是BPA所致DNA损伤的方式之一。5种DNA损伤修复酶表达水平在1μmol/L、10μmol/L、50μmol/L剂量组依次降低,在100μmol/L、100μmol/L+VitC组依次增加,50μmol/L组各种DNA损伤修复酶表达水平最低。BPA50μmol/L组与溶剂对照比较,5种DNA损伤修复酶均有明显降低,差异具有显著性(P<0.05)。100μmol/L组的表达水平均高于50μmol/L组,100μmol/L+VitC组均高于100μmol/L组。除DNA-PKcs与hMSH2外,其他DNA损伤修复酶在100μmol/L+VitC组与溶剂对照组比较差异均无显著性(P>0.05)。[结论]BPA对L-02细胞具有氧化损伤作用,并可导致DNA损伤,多种DNA损伤修复酶参与修复双酚A所导致的DNA损伤。VitC可减缓双酚A的DNA损伤作用。     

维生素E对DNA稳定的影响

维生素E在预防和治疗活性氧自由基(reactive oxygen species，ROS)诱导的DNA损伤、染色体畸变、DNA加合物和微核形成、细胞凋亡，维护细胞DNA稳定等方面具有重要作用，并可作为抗氧化营养素用于人群的干预。尽管许多研究表明，维生素E对DNA稳定有明显保护作用，但也有一些研究显示，无论在体内还是在体外，维生素E均无此作用。     

Effect of Dietary or Supplemental Vitamin C Intake on Vitamin C Levels in Patients with and without Cardiovascular Disease: A Systematic Review

Atherosclerosis is a pro-oxidative and pro-inflammatory disease state, which is the underlying cause of most cardiovascular events, estimated to affect 5.2% of the Australian population. Diet, and specifically vitamin C, through its antioxidant properties can play a role in impeding the development and progression of atherosclerosis. This systematic review conducted comprehensive searches in Medline, Emcare, Scopus, PubMed, and Cochrane using key search terms for vitamin C, plasma vitamin C, supplementation, and cardiovascular disease (CVD). The results demonstrated that vitamin C supplementation resulted in a significant increase in vitamin C levels in populations with or without CVD, except for one study on the CVD population. It was also seen that the healthy population baseline and post-intervention vitamin C levels were high compared to the CVD population. However, further research is indicated for CVD population groups with varying baseline vitamin C levels, such as low baseline vitamin C, within a more representative elderly cohort in order to formulate and update vitamin C repletion guidelines.     

Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model

Sepsis is an extremely complex clinical syndrome, usually involving an excessive inflammatory response including an overshooting cytokine release that damages tissue and organs of the patient. Due to the severity of this condition, it is estimated that over 11 million people die from sepsis each year. Despite intensive research in the field, there is still no specific therapy for sepsis. Many sepsis patients show a marked deficiency of vitamin C. 9 out of 10 sepsis patients have a hypovitaminosis C, and every third patient even shows a clinical deficiency in the scurvy range. In addition, low vitamin C levels of intensive care sepsis patients correlate with a higher need for vasopressors, higher Sequential Organ Failure Assessment (SOFA) scores, and increased mortality. Based on this observation and the conducted clinical trials using vitamin C as sepsis therapy in intensive care patients, the aim of the present ex vivo study was to evaluate the effects of high-dose vitamin C alone and in a triple combination supplemented with vitamin B1 (thiamine) and hydrocortisone on the lipopolysaccharide (LPS)-induced cytokine response in peripheral blood mononuclear cells (PBMCs) from healthy human donors. We found that all corticosteroid combinations strongly reduced the cytokine response on RNA- and protein levels, while high-dose vitamin C alone significantly diminished the PBMC mediated secretion of the cytokines interleukin (IL)-10, IL-23, and monocyte chemo-attractant protein (MCP-1), which mediate the inflammatory response. However, vitamin C showed no enhancing effect on the secretion of further cytokines studied. This data provides important insights into the possible immunomodulatory function of vitamin C in an ex vivo setting of human PBMCs and the modulation of their cytokine profile in the context of sepsis. Since vitamin C is a vital micronutrient, the restoration of physiologically adequate concentrations should be integrated into routine sepsis therapy, and the therapeutic effects of supraphysiological concentrations of vitamin C in sepsis patients should be further investigated in clinical trials.     

抗氧化维生素对苯并(a)芘抑制内皮细胞HSP70表达的干预作用

[目的]研究抗氧化维生素C(Vitamin C，Vit C)和维生素E(Vitamin E，Vit E)对苯并(a)芘(benzo(a)pyrene，BaP)抑制内皮细胞热休克蛋白70(heat shock protein，HSP70)表达的干预作用。[方法]原代培养猪主动脉血管内皮细胞。对照组不染毒，染毒组以不同浓度BaP(0、0．1、0．5、1、5、10μmol/L)染毒24h，VitE和VitC预处理组以100μg／ml的VitE和VitC预处理6h后，再以不同浓度BaP(0、0．1、0．5、1、5、10μmol/L)染毒24h，用Western-blot法检测各组细胞HSP70表达的改变。[结果]BaP抑制了内皮细胞HSP70的表达；VitE和VitC预处理组内皮细胞HSP70表达与对照组相比差别无显著性。[结论]VitE和VitC具有抵抗BaP抑制内皮细胞HSP70表达的效应。     

大剂量维生素C对DNA氧化烷化损伤影响

目的 观察大剂量摄入维生素C（VC）对DNA氧化损伤及烷化损伤的影响。方法以补充大剂量VC饲料给幼年Wistar大鼠，剂量分别为0，2000，5000，10000mg／kg饲料，不添加VC作为对照组，干预时间为60d。干预结束后，采用单细胞凝胶电泳法检测和评价淋巴细胞DNA自发损伤和H202诱导的氧化损伤；留取尿液用毛细管电泳法检测大鼠尿中O^6-甲基鸟嘌呤（O^6-methylguanine,06～MeG）含量。结果各组大鼠的DNA自发损伤差异无统计学意义（P〉0．05）。10μmol／L的H2O2诱发DNA损伤时，随剂量增加，DNA损伤逐渐加重，对照组为59．060AU，2000mg／kg饲料剂量组为69．900AU，5000mg／kg饲料剂量组为75．768AU。比对照组升高28％（P〈0．05），10000mg／kg饲料剂量组为79，655AU，比对照组升高49％（P〈0．01）。各组O^6-MeG的含量差异有统计学意义（P=0．01）。10000mg／kg饲料剂量组含量最高为2．434mg／g肌酐，比对照组升高36％（P〈0．05）。结论高剂量VC对DNA自发损伤没有影响。而对10bμmol／L H2O2的诱导损伤，补充5000mg／kg饲料和10000mg／kg饲料的VC可加重DNA损伤。给大鼠补充10000mg／kg饲料的VC可导致DNA烷化损伤产物O^6-MeG生成增多。     

Effect of Five-Year Supplementation of Vitamin C on Serum Vitamin C Concentration and Consumption of Vegetables and Fruits in Middle-Aged Japanese: A Randomized Controlled Trial

Objective: This study was aimed at evaluating the effect of long-term vitamin C supplementation on serum and dietary vitamin C and identifying the factors associated with change in serum concentration.

Methods: A total of 439 subjects with atrophic gastritis initially participated in a randomized clinical trial using vitamin C and β-carotene to prevent gastric cancer. We originally randomized the participants into four treatment groups using a 2×2 factorial design, whereby 0 or 15 mg/day β-carotene and 50 or 500 mg/day vitamin C were administered in a double-blind manner. The β-carotene component was terminated early after a mean treatment duration of four months. Before and upon early termination of β-carotene supplementation, 134 subjects dropped out this trial, while 120 and 124 subjects took the vitamin C supplement at either 50 mg or 500 mg daily for five years.

Results: Changes in serum vitamin C were significantly higher in the high-dose group (38.5% increase, 95% CI = 27.0–49.9) than in the low-dose group (13.0% increase, 5.1–20.9) or in the dropout group (3.3% increase, ?2.1–8.6) after five-year supplementation. The serum vitamin C at baseline was negatively associated with changes in serum vitamin C (p < 0.0001), while high-dose (p < 0.0001) and low-dose (p < 0.05) supplementation and female gender (p < 0.001) were positively associated. Dietary intake of vitamin C in the supplementation group was almost identical before and after five-year supplementation of vitamin C (2.31 mg/day decrease, 95% CI = ?15.3–10.7), while a 17.7 mg/day decrease (95% CI = ?44.2–8.86) was observed in the drop-out group.

Conclusion: Five-year vitamin C supplementation induces a remarkable increase in serum vitamin C concentration, and our intervention program appears to have no effect on dietary vitamin C intake.     

The Effects of High Concentrations of Vitamin C on Cancer Cells

The effect of high doses of vitamin C for the treatment of cancer has been controversial. Our previous studies, and studies by others, have reported that vitamin C at concentrations of 0.25–1.0 mM induced a dose- and time-dependent inhibition of proliferation in acute myeloid leukemia (AML) cell lines and in leukemic cells from peripheral blood specimens obtained from patients with AML. Treatment of cells with high doses of vitamin C resulted in an immediate increase in intracellular total glutathione content and glutathione-S transferase activity that was accompanied by the uptake of cysteine. These results suggest a new role for high concentrations of vitamin C in modulation of intracellular sulfur containing compounds, such as glutathione and cysteine. This review, discussing biochemical pharmacologic studies, including pharmacogenomic and pharmacoproteomic studies, presents the different pharmacological effects of vitamin C currently under investigation.     

The Effect of Vitamin E and Vitamin C Supplementation on LDL Oxidizability and Neutrophil Respiratory Burst in Young Smokers

Objective: The purpose of this study was to determine the effect of vitamin E and/or vitamin C supplementation on low-density lipoprotein (LDL) oxidizability and neutrophil (PMN) superoxide anion production in young smokers.

Methods: Thirty smokers with a <5 pack-year history were randomly assigned to take placebo; vitamin C (1 g/day); vitamin E (400 IU/day); or both vitamins in a double-blind fashion. Subjects took the supplements for 8 weeks. At weeks 0 and 8, blood was collected for isolation of LDL and PMN, and for antioxidant vitamin analysis. LDL was oxidized with a copper (Cu) catalyst, and oxidation was measured by formation of conjugated dienes over a 5-hour time course. Lag times and maximum oxidation rates were calculated from the time course data. PMN superoxide anion release was assessed by respiratory burst after stimulation with phorbol ester and opsonized zymosan, and their ability to oxidize autologous LDL following treatment with the above stimuli was measured with the conjugated diene assay.

Results: Subjects who received vitamin E alone had a significant increase in the lag phase of Cu-catalyzed LDL oxidation (week 0, 118 ± 31 min vs. week 8, 193 ± 80 min, mean ± SD, p < 0.05), whereas the vitamin C and placebo groups had no changes in LDL oxidation kinetics. The group receiving both vitamins E and C had a significant reduction in oxidation rate (week 0, 7.4 ± 2.3 vs. week 8, 5.1 ± 2.1, p < 0.05). There were no significant changes for any group in PMN superoxide anion production or PMN LDL oxidation after stimulation with either phorbol ester or opsonized zymosan. Plasma and LDL vitamin E concentrations were significantly increased in both groups that received vitamin E. The subjects who received vitamin C alone had no significant change in plasma vitamin C concentrations; however, when data were pooled from both groups who received vitamin C, the increases were significant.

Conclusion: Vitamin E supplementation of young smokers was effective in reducing Cu-catalyzed LDL oxidizability; however, vitamin E and/or C supplementation showed few significant effects on the more physiologically relevant PMN function. This casts doubt on the ability of antioxidant supplementation to reduce oxidative stress in smokers in vivo. Therefore, smoking cessation remains the only means by which young smokers can prevent premature coronary heart disease.     

哺乳动物卵巢储备形成中的DNA损伤修复

在哺乳动物卵巢储备的形成过程中,生殖细胞处于DNA复制、交换和重组的活跃期,对各种内外损伤因素敏感,易发生DNA损伤.多条DNA损伤修复途径在此期间发挥作用.同源重组途径修复DNA双键断裂,保护和重启停滞复制叉;范可尼贫血途径修复链间交联,促进复制叉重启;碱基切除修复途径是全基因组的表观遗传编程的重要机制;错配修复途径...     

氯乙烯致大鼠DNA损伤与DNA损伤修复酶和p53蛋白的表达

目的研究氯乙烯（VC）对大鼠原代肝细胞DNA的损伤作用,及对DNA损伤修复酶（rMSH2和XPD）和抑癌蛋白p53表达的影响;探索VC所致DNA损伤的修复和调控机制。方法大鼠腹腔注射VC,隔日染毒,染毒剂量分别为5,10和20mg／kg。单细胞凝胶电泳测肝细胞DNA损伤,免疫组化法测肝脏DNA损伤修复酶的表达。结果彗星细胞数目随染毒剂量增加而增加,彗星发生率与VC染毒剂量问存在明显的相关关系。rMSH2表达随染毒剂量增加而减少．XPD和p53的表达随染毒剂量增加而增加。VC致DNA损伤与XPD表达具有相关关系。结论VC可导致肝细胞DNA发生损伤,且存在剂量一反应关系;DNA损伤修复酶和p53蛋白参与修复VC所致的DNA损伤。     

香烟烟雾对2种肺细胞的DNA损伤与修复

目的探讨经香烟烟雾溶液染毒的人正常肺间质细胞和人肺腺癌细胞的DNA损伤及其修复效应.方法体外培养人胚肺成纤维细胞(HLF)和人肺腺癌A549细胞,以二甲基亚砜(DMSO)和磷酸缓冲液(PBS)作为吸收液,采集香烟主流烟雾.用四甲基偶氮唑盐(MTT)法测定香烟烟雾-DMSO吸收液和香烟烟雾-PBS吸收液(分别简称DMSO烟液和PBS烟液)的1/2、1/4、1/8和1/16倍稀释液和原液对HLF细胞和A549细胞的毒性(分别以DMSO和PBS为阴性对照),以无明显细胞毒性的浓度进行彗星实验(分别以DMSO和PBS为阴性对照,以重铬酸钾为阳性对照),测定细胞的DNA损伤及修复情况.结果DMSO烟液原液及其1/2稀释液染毒的细胞存活率低于80%,而PBS烟液染毒的细胞存活率均高于80%.DMSO烟液的1/4、1/8、1/16倍稀释液以及PBS烟液的1/2、1/4、1/8和1/16倍稀释液和原液对HLF细胞和A549细胞的DNA损伤与阴性对照组相比,差异均具有统计学意义(P＜0.01),且存在明显的剂量-效应关系.DNA损伤在两种细胞间差异无统计学意义(P＞0.05),但DMSO烟液所致的DNA损伤高于PBS烟液(P＜0.01).细胞在去除受试物后培养30 min时开始修复,随着修复时间的延长,拖尾细胞数减少,DNA迁移长度缩短(P＜0.05),且A549细胞修复得更快(P＜0.05).结论DMSO烟液的细胞毒性和遗传毒性均高于PBS烟液.香烟烟雾对HLF细胞和A549细胞的DNA损伤差异不明显,A549细胞的DNA损伤修复能力较HLF细胞强.     

Effect of Vitamin C on Tendinopathy Recovery: A Scoping Review

Tendinopathies represent 30–50% of all sports injuries. The tendon response is influenced by the load (volume, intensity, and frequency) that the tendon support, resulting in irritability and pain, among others. The main molecular component of tendons is collagen I (60–85%). The rest consist of glycosaminoglycans-proteoglycans, glycoproteins, and other collagen subtypes. This study’s aim was to critically evaluate the efficacy of vitamin C supplementation in the treatment of tendinopathies. At the same time, the study aims to determine the optimal conditions (dose and time) for vitamin C supplementation. A structured search was carried out in the SCOPUS, Medline (PubMed), and Web of Science (WOS) databases. The inclusion criteria took into account studies describing optimal tendon recovery when using vitamin C alone or in combination with other compounds. The study design was considered, including randomized, double-blind controlled, and parallel designs in animal models or humans. The main outcome is that vitamin C supplementation is potentially useful as a therapeutic approach for tendinopathy recovery. Vitamin C supplementation, alone or in combination with other products, increases collagen synthesis with a consequent improvement in the patient’s condition. On the other hand, vitamin C deficiency is mainly associated with a decrease in procollagen synthesis and reduced hydroxylation of proline and lysine residues, hindering the tendon repair process.     

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

This paper reviews the possible origin of sperm DNA fragmentation and focuses on the nuclear events associated with spermiogenesis as a potential source of genetic instability and reduced fertilizing potential of the mature male gamete. Recent findings suggest a programmed DNA fragmentation and DNA damage response during the chromatin remodeling steps in spermatids. We also discuss the spermatid DNA repair mechanisms and the possible involvement of condensing proteins, such as transition proteins and protamines, in the process, as this DNA fragmentation is normally not found in late spermatids. We propose that alterations in the chromatin remodeling steps or DNA repair in elongating spermatids may lead to persistent DNA breaks. This vulnerable step of spermiogenesis may provide a clue to the etiology of sperm DNA fragmentation associated with infertility in humans. This vulnerability is further emphasized given the haploid character of spermatids that must resolve programmed double-stranded breaks by an error-prone DNA repair mechanism. Therefore, spermiogenesis has probably been overlooked as an important source of genetic instability.     

Estimation of Vitamin C Intake Requirements Based on Body Weight: Implications for Obesity

Higher body weight is known to negatively impact plasma vitamin C status. However, despite this well-documented inverse association, recommendations on daily vitamin C intakes by health authorities worldwide do not include particular reference values for people of higher body weight. This suggests that people of higher body weight and people with obesity may be receiving insufficient vitamin C in spite of ingesting the amounts recommended by their health authorities. The current preliminary investigation sought to estimate how much additional vitamin C people with higher body weights would need to consume in order to attain a comparable vitamin C status to that of a lower weight person consuming an average Western vitamin C intake. Data from two published vitamin C dose-concentration studies were used to generate the relationship: a detailed pharmacokinetic study with seven healthy non-smoking men and a multiple depletion–repletion study with 68 healthy non-smoking men of varying body weights. Our estimates suggest that an additional intake of 10 mg vitamin C/day is required for every 10 kg increase in body weight to attain a comparable plasma concentration to a 60 kg individual with a vitamin C intake of ~110 mg/day, which is the daily intake recommended by the European Food Safety Authority (EFSA). Thus, individuals weighing e.g., 80 and 90 kg will need to consume ~130 and 140 mg vitamin C/day, respectively. People with obesity will likely need even higher vitamin C intakes. As poor vitamin C status is associated with increased risk of several chronic diseases including cardiovascular disease, these findings may have important public health implications. As such, dose-finding studies are required to determine optimal vitamin C intakes for overweight and obese people.     

甲基汞对雄性生殖细胞DNA合成及其修复合成的作用

为深入了解甲基汞的遗传毒性和生殖毒性，采用氚标胸腺嘧啶核苷（３Ｈ－ＴｄＲ）掺入法和体内程序外ＤＮＡ修复合成（ＵＤＳ）研究了甲基汞对雄性生殖细胞ＤＮＡ合成及其修复合成的影响。结果表明：甲基汞可以抑制雄性生殖细胞ＤＮＡ合成，损伤生殖细胞ＤＮＡ，造成程序外ＤＮＡ修复合成的增加。甲基汞对ＤＮＡ合成的损伤作用与染毒剂量有关。同时，对甲基汞影响雄性生殖细胞ＤＮＡ合成及修复合成的机制进行了探讨。