Cytotoxicity of cigarette smoke condensate is not due to DNA double strand breaks: Comparative studies using radiosensitive mutant and wild-type CHO cells

Purpose:?To determine whether cigarette smoke condensate (CSC) without metabolic activation induces direct DNA double strand breaks (DSB) in the G1 phase of various radiosensitive mutants of CHO cells and whether these breaks display collateral hypersensitivity to CSC with respect to cell killing.

Materials & methods:?We treated the G1-phase cultures of wild-type and DNA repair deficient mutants of CHO cells with various concentrations of CSC and examined the cell survival by colony formation assay and the induction of DNA double strand breaks by constant field gel electrophoresis as well as the phophorylated histone H2-A variant X (γ-H2AX) assay.

Results:?Gel analysis and γ-H2AX focus assay showed significantly fewer, but still detectable levels of DSB per cell after CSC treatment compared to ionizing radiation (IR) exposures, even when equitoxic radiation exposures were delivered at a low dose rate over the same 8-hour exposure used for CSC treatments. None of the three non-homologous end joining (NHEJ) deficient mutants were remarkably hypersensitive to CSC compared to wild-type cells. In contrast, UV-1 cells that are hypersensitive to several base damage and cross-linking agents showed a higher sensitivity to CSC compared to the other CHO cell lines.

Conclusions:?DNA DSB produced directly by CSC are not principally responsible for its cytotoxicity. Further, the present study does not rule out the possibility that some of these lesions may secondarily result in DSB, such as may occur during impeded DNA replication and whose repair may require systems other than NHEJ.     

Gestational Exposure of Mice to Secondhand Cigarette Smoke Causes Bronchopulmonary Dysplasia Blocked by the Nicotinic Receptor Antagonist Mecamylamine

Background: Cigarette smoke (CS) exposure during gestation may increase the risk of bronchopulmonary dysplasia (BPD)—a developmental lung condition primarily seen in neonates that is characterized by hypoalveolarization, decreased angiogenesis, and diminished surfactant protein production and may increase the risk of chronic obstructive pulmonary disease.Objective: We investigated whether gestational exposure to secondhand CS (SS) induced BPD and sought to ascertain the role of nicotinic acetylcholine receptors (nAChRs) in this response.Methods: We exposed BALB/c and C57BL/6 mice to filtered air (control) or SS throughout the gestation period or postnatally up to 10 weeks. Lungs were examined at 7 days, 10 weeks, and 8 months after birth.Results: Gestational but not postnatal exposure to SS caused a typical BPD-like condition: suppressed angiogenesis [decreased vascular endothelial growth factor (VEGF), VEGF receptor, and CD34/CD31 (hematopoietic progenitor cell marker/endothelial cell marker)], irreversible hypoalveolarization, and significantly decreased levels of Clara cells, Clara cell secretory protein, and surfactant proteins B and C, without affecting airway ciliated cells. Importantly, concomitant exposure to SS and the nAChR antagonist mecamylamine during gestation blocked the development of BPD.Conclusions: Gestational exposure to SS irreversibly disrupts lung development leading to a BPD-like condition with hypoalveolarization, decreased angiogenesis, and diminished lung secretory function. Nicotinic receptors are critical in the induction of gestational SS–induced BPD, and the use of nAChR antagonists during pregnancy may block CS-induced BPD.     

卷烟烟气抽提物对细胞遗传毒性及茶多酚干预作用

目的探讨卷烟烟气抽提物(CSE)对支气管上皮细胞(BEAS-2B)遗传毒性及茶多酚干预作用。方法以高、中、低3个浓度对支气管上皮细胞进行染毒,同时设立茶多酚干预组和空白对照组;采用彗星实验及γ-H2AX蛋白表达检测DNA损伤,以微核实验检测染色体损伤,并检测HPRT基因突变率。结果高剂量染毒组BE-AS-2B细胞彗星细胞数(130.5±1.6)个、彗星尾长(134.33±3.56)μm、尾部面积(7 798.43±43.45)μm2,均明显高于空白对照组(P<0.05),并呈剂量—效应关系;CSE低、中、高剂量染毒组BEAS-2B细胞中微核细胞分别为(22.4±3.2)、(38.6±1.8)、(79.6±2.4)个,均明显多于空白对照组的(6.2±1.5)个(P<0.05);CSC中、高剂量染毒组BEAS-2B细胞HPRT基因突变率分别为(0.802±0.040)‰、(1.058±0.002)‰,均明显高于空白对照组的(0.330±0.002)‰(P<0.05)。茶多酚对CSE诱发的DNA链断裂及微核细胞增多有明显抑制作用,并可有效降低HPRT基因突变率。结论 CSE具有细胞遗传毒性,茶多酚对其遗传毒性具有干预作用。     

Skin aging induced by ultraviolet exposure and tobacco smoking: evidence from epidemiological and molecular studies

BACKGROUND: Tobacco smoking, similar to ultraviolet (UV) A radiation exposure, has previously been identified as an important factor contributing to premature aging of human skin. OBJECTIVE AND DESIGN: To investigate the relationship between these two environmental factors, we have conducted a cross-sectional study of 83 subjects (48 males, 35 females, age range 23-95), in which sun exposure, pack-years of smoking history and potential confounding variables were assessed by questionnaire. Facial wrinkles were quantified using the Daniell score. In order to study the molecular mechanism by which smoking caused wrinkle formation, in vitro studies were conducted to assess the alteration of matrix metalloproteinase-1 (MMP-1) mRNA expression in human fibroblasts stimulated with tobacco smoke extract or/and UVA. RESULTS: Logistic statistic analysis of the data revealed that age [odds ratio (OR)=7.5, 95% confidence interval (CI)=1.87-30.161, pack-years (OR=5.8, 95% CI=1.72-19.87), and sun exposure (OR=2.65, 95% CI=1.0-7.0) independently contributed to facial wrinkle formation. When excessive sun exposure (>2 h/day) and heavy smoking (35 pack-years) occurred together, the risk for developing wrinkles was 11.4 times higher than that of non-smokers and those with less sun exposure (<2 h/day) at the same age. The in vitro studies revealed that MMP-1 expression was significantly increased in fibroblasts after the stimulation with either tobacco smoke extract or UVA. Maximum induction was observed when cells were treated with tobacco smoke extract plus UVA, indicating that the two factors act in an additive manner. MMP-1 induction was significantly higher in the low glutathione (GSH) content fibroblast compared to that in the high GSH fibroblast, indicating that the differences in glutathione content define the susceptibility of fibroblasts towards UV- or tobacco smoking-induced MMP-1 expression. CONCLUSION: Tobacco smoke and UVA cause wrinkle formation independently of each other. We propose that both factors cause aging of human skin through additive induction of MMP-1 expression.     

Tobacco smoke is phototoxic

BACKGROUND: Both cigarette smoke and ultraviolet (UV) radiation are known to cause changes of the skin which can be regarded as premature ageing. OBJECTIVES: To assess the theory that the effects of these two exposures could be linked by a phototoxic action of cigarette smoke. METHODS: A photohaemolysis test was used, in which human erythrocytes were incubated with cigarette smoke condensate, followed by UV irradiation and measurement of exposure-dependent haemolysis. RESULTS: Cigarette smoke condensate was clearly phototoxic. Photohaemolysis depended on the concentration of the condensate and UV dose and was more pronounced after exposure to UVA-rich than UVB-rich radiation. CONCLUSIONS: Phototoxicity may be a mechanism by which cigarette smoking causes premature skin ageing. An enhancing effect on photocarcinogenesis has also to be considered.     

Passive smoke exposure is associated with perioperative adverse effects in children

Study Objective

To evaluate the frequency of respiratory adverse events during general anesthesia in children passively exposed to cigarette smoke (PSE).

Design

Prospective, double blinded, observational study.

Setting

Operating room and recovery room of a university hospital.

Measurements

Data were collected from 385 children who underwent elective surgery during general anesthesia from June to November, 2008. PSE was identified by using the child's caregivers' information. Respiratory adverse events were recorded during anesthesia and post-anesthesia.

Main Results

Technique of anesthesia induction and management, distribution of patients' age, gender, surgical procedures, and perioperative analgesic methods were similar in the PSE and non-PSE groups. Respiratory adverse events were reported in 58 patients (15.1%): 50 patients (21.4%) were in the PSE and 8 patients (5.3%) were in the non-PSE group (P = 0.00). The frequency of laryngospasm during anesthesia (P = 0.03) and hypersecretions in the recovery room (P = 0.00) were significantly increased in the PSE group.

Conclusions

Children who are exposed to environmental tobacco smoke and who undergo general anesthesia seem to have an increased risk of respiratory complications in the recovery period rather than during anesthesia.     

吸烟对甲状腺相关眼病患者斜视手术影响

目的 探讨不同吸烟状态对甲状腺相关眼病患者斜视手术的影响.方法 对2000年1月至2009年12月在上海长征医院眼科住院的甲状腺相关眼病患者进行随访,比较不同吸烟状态患者的基本资料、临床数据及术后二次手术情况.结果 在208例接受斜视手术的甲状腺相关眼病患者中,55例为不吸烟者,40例为被动吸烟者,21例为曾吸烟者,81例为吸烟者,未记录者11例.264例吸烟患者中81例接受了斜视手术.而338例不吸烟患者中仅55例接受了斜视手术(P=0.038).曾吸烟患者对比不吸烟患者,其风险比为1.121;被动吸烟患者对比不吸烟患者,其风险比为1.595,差异均没有统计学意义.性别及甲状腺功能状态对斜视的影响差异无统计学意义.结论 吸烟增加甲状腺相关眼病患者接受斜视手术的几率,同时会增加二次手术的概率.     

艾烟的急性毒理试验

以湖南中医药大学无特定病原体级（Specific Pathogen Free,SPF）Sprague-Dawley（SD）大鼠为试验对象,进行艾烟的急性毒理试验,结果表明：艾烟对大鼠的半数致死浓度LC50为11117mg/m3,根据世界卫生组织（WHO）的标准得出艾烟的毒性分级为微毒。     

Driving kids to smoke? Children's reported exposure to smoke in cars and early smoking initiation

The health risks associated with second hand smoke (SHS) are well-known. However, little is known about exposure to SHS in cars and risk of smoking uptake. This paper investigates the association between pre-adolescents reported exposure to smoking in cars and prevalence of early stage smoking activity. Data from Keeping Kids Smokefree baseline surveys of students were used to investigate smoking status and reported exposure to smoking in cars. Log binomial regression analyses were used to investigate if reported exposure to SHS in cars was associated with smoking prevalence. 83% of 5676 students invited took part. After controlling for all variables reported exposure to smoking in cars and homes were significantly associated with increased risk of initiated smoking (RR 1.87, 95% CI 1.43-2.44, and RR 1.5, 95% CI 1.13-1.97, respectively). Exposure to smoking in cars was substantially and significantly associated with risk of current smoking (RR 3.21, 95% CI 1.45-7.08). Early smoking uptake is associated with students' reported exposure to smoking in cars which confirms the importance of protecting children from SHS. Smoking in cars is under parental control and therefore modifiable. Moreover, children's reports of SHlS exposure offer a simple way of identifying families who can be targeted for tobacco control interventions.