利用Tox21通路数据库评估石家庄市大气细颗粒物中多环芳烃激活毒性通路的风险

目的： 采用Tox21毒性检测数据库中通路数据对2017年石家庄市供暖期大气细颗粒物（PM_2.5）中多环芳烃（PAHs）的检测数据进行分析计算，评估PM_2.5引起毒性通路激活的风险。方法： 在石家庄市河北医科大学远离工业污染源设置1个采样点收集大气PM_2.5，通过气相色谱-串联质谱法（GC-MS）检测美国环境保护署优先控制的16种PAHs的浓度。利用MPPD软件计算各PAHs单体在成人肺泡中的沉积量；检索Tox21毒性检测数据库中芳烃受体（AhR）、核因子E2相关因子（Nrf2）、p53和核因子κB（NF-κB）各通路的剂量反应关系数据，计算各PAHs单体激活各通路的单位强度；结合PAHs在肺泡的沉积量和PAHs激活通路的强度，评估PM_2.5激活各个通路的风险。结果： 石家庄市供暖期PM_2.5中PAHs检测结果显示，苯并[a]芘的日均浓度为9.13 ng/m³，日均浓度排名前3的苯并[b]荧蒽、荧蒽和芘的浓度分别为22.88、17.86及14.31 ng/m³。这16种PAHs以苯并[a]芘为参照的毒性当量浓度为17.74 ng/m³。毒性通路激活风险预测结果提示激活强度最大的是NF-κB通路，其次是AhR、Nrf2，p53被激活的可能性最弱，其中相对应的活性暴露比（AER）值分别为1.97、1.71、0.58和0.28。结论： 石家庄市大气细颗粒物中PAHs的暴露，可能通过激活NF-κB和AhR信号通路增加致癌风险。     

In Utero Exposure to Benzo[a]pyrene Induces Ovarian Mutations at Doses That Deplete Ovarian Follicles in Mice

Polycyclic aromatic hydrocarbons like benzo[a]pyrene (BaP) are ubiquitous environmental contaminants formed during incomplete combustion of organic materials. Our prior work showed that transplacental exposure to BaP depletes ovarian follicles and increases prevalence of epithelial ovarian tumors later in life. We used the MutaMouse transgenic rodent model to address the hypothesis that ovarian mutations play a role in tumorigenesis caused by prenatal exposure to BaP. Pregnant MutaMouse females were treated with 0, 10, 20, or 40 mg/(kg day) BaP orally on gestational days 7–16, covering critical windows of ovarian development. Female offspring were euthanized at 10 weeks of age; some ovaries with oviducts were processed for follicle counting; other ovaries/oviducts and bone marrow were processed for determination of lacZ mutant frequency (MF). Mutant plaques were pooled within dose groups and sequenced to determine the mutation spectrum. BaP exposure caused highly significant dose-related decreases in ovarian follicles and increases in ovarian/oviductal and bone marrow mutant frequencies at all doses. Absence of follicles, cell packets, and epithelial tubular structures were observed with 20 and 40 mg/(kg day) BaP. Depletion of ovarian germ cells was inversely associated with ovarian MF. BaP induced primarily G > T and G > C transversions and deletions in ovaries/oviducts and bone marrow cells and produced a mutation signature highly consistent with that of tobacco smoking in human cancers. Overall, our results show that prenatal BaP exposure significantly depletes ovarian germ cells, causes histopathological abnormalities, and increases the burden of ovarian/oviductal mutations, which may be involved in pathogenesis of epithelial ovarian tumors. Environ. Mol. Mutagen. 60:410–420, 2019. © 2018 Her Majesty the Queen in Right of Canada     

Influence of postnatal polycyclic aromatic hydrocarbon exposure on the neurodevelopment of toddlers at the age of 12 months

ObjectivesTo investigate the possible influence of polycyclic aromatic hydrocarbons (PAHs) exposure on neurodevelopment of toddlers at the age of 12 months.MethodsTotally 306 subjects were recruited from the Qingdao Birth Cohort established in 2014. PAH-DNA adducts in toddlers’ umbilical cord blood samples, hydroxyl-PAH metabolites in their urine samples and the developmental quotients (DQs) were measured. Sex, gestational age, birth weight, and maternal educational background were adjusted to analyze the influence of the PAH exposure on the neurodevelopment of the toddlers using multivariate linear regression model.ResultsPearson correlation test showed that the logarithmic values of hydroxyl-PAH were negatively correlated with the DQs. Multivariate linear regression analysis indicated that logarithmic concentration of 1(9)- hydroxyphenanthrene was still associated with the DQs of the fine motor behaviors with β and 95% confidential interval (CI) of -1.137 (-2.053, -0.222), together with PAH-DNA adducts [β (95% CI): -0.577 (-0.930, -0.225)]. PAH-DNA adducts presented an independently negative influence on the DQs of the gross motor and personal social behaviors with β (95%CI) of -0.470 (-0.814, -0.126) and -0.526 (-0.859, -0.193), respectively.ConclusionsThe exposure to PAHs in toddlers at 12 months could influence their neurodevelopment. Additionally, prenatal exposure to PAHs should also be considered.     

Determination of polycyclic aromatic hydrocarbons (PAHs) in cosmetic products by gas chromatography-tandem mass spectrometry

A gas chromatography coupled with tandem mass spectrometry (GC-MS/MS) method is developed to determine 18 representative polycyclic aromatic hydrocarbons (PAHs) in cosmetics, including Benzo[a]pyrene (BaP) and others. The method offers high sensitivity and selectivity under selected reaction monitoring (SRM) mode to satisfy the requirements of both quantitation and qualitation. The extraction solvent system used in this study is acetone/hexane 1:1 (v/v) and other purification procedure is unnecessary. The linearities of 18 PAHs are validated in different concentration in the range of 0.25–20 ng/mL individually with coefficient correlation (r) higher than 0.996. The recoveries for spiking 3 different concentrations are from 87.40% to 120.44% for 18 PAHs and the coefficient of variation (CV) are below 12.32%. Limit of quantification (LOQ) of 18 PAHs is in the range of 0.05–0.2 mg/kg. A matrix enhancement effect is observed and can be compensated with deuterated internal standard. The method has been successfully applied to 73 samples, over 40 of them are lipsticks. The results show none of the samples detect Benzo[a]pyrene (BaP) and Dibenzo[a,h]anthracene (DBA), both are classified as the most carcinogenic. 8 PAHs are detected and the average value between 0.08 and 0.27 mg/kg. This study offers a sensitive and simple method to analyze 18 representative PAHs successfully and can be applied to cosmetic products and raw materials.     

口腔黏膜上皮细胞体外癌变模型的建立

目的诱导永生化口腔上皮细胞系（HIOEC）细胞恶性转化，建立口腔黏膜上皮细胞体外癌变模型。方法通过化学致癌剂苯并芘[B（a）P]体外诱导HIOEC细胞，逐步筛选到鳞状细胞癌细胞系HIOEC-B（a）P。通过微分干涉显微镜和HE染色观察细胞形态学改变；用软琼脂集落形成及裸小鼠异体皮下成瘤的实验鉴定HIOEC-B（a）P细胞的恶性表型。结果①HIOEC细胞在B（a）P诱导培养后可以在正常生理钙离子浓度、含胎牛血清培养液中生长；②细胞在诱导过程中形态多变，最后稳定为多角形铺路石样上皮细胞；③第93代HIOEC-B（a）P细胞开始具备软琼脂集落形成能力；④HIOEC—B（a）P第55代细胞在裸小鼠皮下首次形成角化团块，第69代细胞形成分化较好的典型鳞状细胞癌，第74代、第96代细胞均形成与临床病理相似的Ⅰ～Ⅱ级鳞状细胞癌。结论生物因素合并化学致癌因素B（a）P可以诱导永生化口腔黏膜上皮细胞恶性转化，为进一步研究口腔黏膜上皮细胞多因素、多步骤癌变机制提供实验模型。     

Comparative unsupervised clinical trial on caries inhibition effect of monofluorophosphate and amine fluoride dentifrices after 3 years in Strasbourg, France

A randomized, double blind clinical trial of the caries inhibition effects of dentifrices containing respectively monofluorophosphate and amine fluoride was performed. A third control group used a toothpaste without fluoride. A total number of 2008 schoolchildren ranging in age from 6 to 8 years and living in Strasbourg (France) participated in this study. After a baseline examination three groups were constructed with the block randomization technic. The caries inhibition effects of the three dental pastes were compared after 3 years of unsupervised use. The monofluorophosphate dentifrice showed a reduction of 7.02% for DMFT, 5.17% for DMFS and 25.26% for the df rate. The reduction of amine fluoride dentifrice caries was respectively 21.62% for DMFT, 20.94% for DMFS and 48.66% for the df rate.     

Plaque and gingivitis in the elderly: a randomized, single-blind clinical trial on the outcome of intensified mechanical or antibacterial oral hygiene measures

OBJECTIVES: To study the outcome of intensified mechanical oral hygiene compared with the effect of an adjunctive antibacterial mouth rinse on plaque and gingivitis in elderly people. MATERIAL AND METHODS: In a randomized, single-blind, 6-month controlled clinical study, 106 subjects, 55 years or older, were divided into four groups: (I) Participants were instructed on improved mechanical oral hygiene, including interdental hygiene; (II) subjects used an antibacterial mouth rinse containing amine and stannous fluoride in addition to their usual oral hygiene practices; (III) both intensive mechanical and antibacterial measures were combined; and (IV) a control group with no specific regimen. Gingivitis and plaque were examined. RESULTS: After 6 months, both plaque and gingivitis scores were significantly lower than at baseline in all groups. Reductions in gingivitis differed significantly between the control group and all other groups but not between the three intervention groups. Only groups with improved mechanical oral hygiene showed significant improvements in plaque scores compared with control. CONCLUSIONS: Intensive mechanical oral hygiene resulted in greater plaque reduction than the combination of an antibacterial rinse and usual oral hygiene procedures. Gingivitis was reduced by both intensive oral hygiene and use of the amine/stannous fluoride rinse. Combining intensive mechanical oral hygiene with the antibacterial rinse did not result in further gingivitis reduction.     

A comparison of the plaque-inhibitory properties of stannous fluoride and low-concentration chlorhexidine mouthrinses

BACKGROUND: Plaque inhibition by chlorhexidine (CHX) rinses is dose related with a relatively flat dose-response curve above 5-6 mg twice daily. Low dose regimens could therefore reduce local side effects but maintain reasonable efficacy. AIMS: To compare the plaque inhibitory properties of two low-dose CHX rinse products with more conventional levels delivered from proprietary rinses. A secondary outcome was a comparison with a stannous fluoride/amine fluoride (SFAF) rinse product. METHODS: The study was a five-treatments, negative controlled, randomised, single blind crossover design balanced for residual effects, involving 20 healthy subjects in a 24-h plaque re-growth model. On day 1 of each study period, subjects were rendered plaque free, suspended tooth cleaning and followed the appropriate rinse regimen. On day 2, subjects were scored for plaque by index and area. The rinse codes and rinsing regimens were: (A) 15 mg CHX 2 x daily for 30 s (0.1% CHX), (B) 9 mg CHX 2 x daily for 60 s (0.06% CHX), (C) 10 ml SFAF rinse 1 x daily for 30 s, (D) 15 ml placebo 2 x daily for 60 s, and (E) 6 mg CHX 2 x daily for 30 s (0.06% CHX). RESULTS: Average mouth plaque indices and areas were highly significantly different between rinsing regimens. All test rinses were significantly more effective than the placebo rinse. There was a mean dose-response pattern for the CHX rinses, but there were no statistically significant differences between any of the test rinses. CONCLUSIONS: Lower doses of chlorhexidine in rinses can be used to exert plaque inhibition comparable with products used at higher doses and equivalent to benchmark products such as the SFAF rinse. However, the availability of chlorhexidine from formulations has to be considered as in part explaining the results.