In vitro exposure to cigarette smoke induces oxidative stress in follicular cells of F1 hybrid mice

Health Canada is responsible for the regulation of tobacco products and controlled substances, and conducts research on the health consequences of tobacco use to inform and support this regulatory role.  One consequence of tobacco use is reduced fertility in women. Understanding the mechanisms that cause reduced fertility may enable the development of more informed guidelines on the risks of tobacco use. In this study, Health Canada, in collaboration with researchers from McMaster University, examined the impact of chemicals found in cigarette smoke on mouse follicular cells. These cells are derived from follicles, which are structures within the ovary that contain a single egg. Proper follicular cell function is thus critical in female reproductive health. Specifically, Health Canada examined whether chemicals found in tobacco smoke cause oxidative stress in the cells. Oxidative stress is an umbrella term that refers to various types of cellular damage caused by chemically-reactive molecules that contain oxygen, and which can potentially lead to cell death or other forms of damage. The results showed that exposure to the chemicals from cigarette smoke did result in oxidative stress within the follicular cells, and that higher levels of chemical exposure resulted in the highest levels of oxidative stress. These data mean that reduced fertility in women exposed to cigarette smoke may be due, in part, to oxidative stress in follicular cells. Health Canada will use the results of this study to better understand the health risks associated with exposure to cigarette smoke. Results of this research are published in the
Journal of Applied Toxicology,
2014, 34(2), 224-226.

A Global Toxicogenomic Analysis Investigating the Mechanistic Differences between Tobacco and Marijuana Smoke Condensates in vitro

Health Canada promotes the prevention and cessation of marijuana smoking through the National Anti-Drug Strategy. Although youth perceive marijuana to be a "natural" product that is less harmful than smoking tobacco, habitual marijuana smoking has also been shown to result in adverse pulmonary effects. The mechanisms underlying these adverse effects, however, have not been well characterised. In this study, Health Canada compared marijuana smoke condensate (MSC) and tobacco smoke condensate (TSC) in order to examine their effects on gene expression using cultured mouse lung cells. The results showed that MSC affects many of the same genes and cellular processes as TSC (e.g., inflammation, DNA damage response), and in many cases is more potent than TSC. The results of this study provide further evidence that smoking marijuana can have harmful health effects. Health Canada will use the results of this study to help inform Canadians of the hazards of smoking marijuana. Results of this research are published in Toxicology, 2013, 308, 60-73.

IL-1 Receptor Regulates microRNA-135b Expression in a Negative Feedback Mechanism during Cigarette Smoke-Induced Inflammation

Health Canada helps protect and promote health by using existing legislative and regulatory frameworks to mitigate the potential health risks of toxicant exposure. In previous studies, Health Canada scientists found that inhalation of small particles caused lung inflammation in mice, and that this inflammation was accompanied by very large changes in a molecule called microRNA-135b (miR-135b). MiR-135b was particularly responsive in the lungs of mice exposed to very small particles called nanoparticles. In this follow up study, Health Canada scientists collaborated with researchers from McMaster University to conduct a series of experiments in mice and cells in culture to investigate if the type of inflammation that is associated with response of miR-135b is comparable to inflammation induced by another environmental particle (cigarette smoke) or is more similar to the type of inflammation induced by a bacterial infection. The work aimed to determine the significance of changes in miR-135b to lung injury caused by nanoparticles. Mice were exposed to cigarette smoke or non typeable haemophilus influenzae bacteria, and lung inflammation was characterised. The results revealed that inflammation processes induced in response to cigarette smoke are the same as those identified previously following exposure to nanoparticles and that they are mediated by miR-135b. The investigators identified the IL-1 receptor gene as an important regulator of this inflammation. Follow up studies are being conducted to determine if miR-135b expression can be used to classify the type of inflammatory responses observed in mice following particle exposure, with a focus on the use of miR-135b in evaluating the potential toxicity of diverse types of nanoparticles being used in commerce today. The results of this research are published in the Journal of Immunology, 2013, 190(7), 3679-3686.

Mutagenicity of Smoke Condensates from Canadian Cigarettes with Different Design Features

Health Canada works in partnership with all levels of government, the health community and other stakeholders to protect Canadians from the hazards and risks to health associated with tobacco. The vast majority of cigarettes sold in Canada are similar in design. For example, most cigarettes have similar dimensions (length and diameter), a cellulose-acetate filter, and contain a single type of tobacco called ‘Virginia flue-cured’ tobacco. Cigarette brands with different design features have become available in the Canadian market yet there is little that is known about how changing the design of a cigarette may affect its toxicity. In this Health Canada study, a specific measure of toxicity known as gene mutation was evaluated for 11 commercial brands of Canadian cigarettes. Cigarettes with different filters (charcoal or MicroBlue™), a super slim design, or tobacco blends that contain a mixture of tobacco types were compared to those that have traditionally been found in the Canadian market. Cigarette smoke condensates were collected from the cigarettes using two different machine smoking conditions: the International Organisation for Standardisation and the Health Canada Intense smoking regimes. The condensates were used to determine the potential of the different cigarettes to produce DNA damage that leads to gene mutations using a cell-based assay called the ‘Salmonella mutagenicity assay’. Using three different types of Salmonella the commercial brands were compared to two reference cigarettes and a Canadian best seller. The results showed there is no significant difference in the ability of cigarettes with the different filters to cause gene mutations. While the super slim design did provide some reduction in the potential to cause gene mutations for some of the brands studied, it is important to note that human exposure and smoking behaviour were not included in the study and the reduction in mutagenic potency cannot be interpreted as reduction in harm. Health Canada will use the results of this study to inform future developments in policy and tobacco regulations. Research results are published in Mutagenesis (2014) vol. 29 pg. 7-15.

Assessment of Validity of Self-Reported Smoking Status

Smoking cigarettes is associated with numerous adverse health effects, including cancer, respiratory illness, heart disease and stroke. Health Canada is committed to reducing disease and death attributable to tobacco use among Canadians. In Canada, national smoking prevalence data, which is the percentage of Canadians who smoke, is generally based on self report through personal interviews. However, it is not yet known whether estimates of cigarette smoking based on self-reported data is valid. Statistics Canada and Health Canada recently examined the validity of self-reported smoking status by comparing estimates of smoking prevalence based on self-report with estimates based on the measurement of cotinine in the urine. Cotinine is the major breakdown product of nicotine metabolism. The measurement of cotinine in urine is an accepted, objective measure of exposure to tobacco smoke and provides an alternate approach to obtaining smoking prevalence data. Data were from the 2007-2009 Canadian Health Measures Survey, a nationally representative cross-sectional survey, which included self-reported smoking status and the measurement of urinary cotinine for 4,530 Canadians aged 12-79. Results from this study showed no significant difference between national estimates of smoking prevalence based on self report vs. urinary cotinine concentrations, and suggest that smoking prevalence based on self report provides a valid estimate of smoking prevalence in Canada. Results of this research are published in Health Reports, Component of Statistics Canada Catalogue no. 82-003-X.

Sidestream Tobacco Smoke is a Male Germ Cell Mutagen

Health Canada is responsible for implementing and promoting initiatives that reduce or prevent the negative health impacts associated with smoking. Despite years of an intense public campaign to limit and reduce tobacco consumption, cigarette smoking is still widespread and its health effects remain a significant public health concern. More than a third of men of reproductive age are smokers. Previous studies have shown that these men are at higher risk of having sperm defects, including DNA damage and mutations that could cause miscarriages and birth defects in their children. Much less is known about the reproductive consequences of exposure to second-hand smoke. In order to better understand the impacts of environmental factors, such as second-hand smoke, on sperm, scientists at Health Canada and the Lawrence Berkeley National Laboratory measured changes in DNA in the sperm of mice exposed to second-hand tobacco smoke. DNA damage in sperm is particularly important to understand because it can be passed on to offspring and result in harmful effects, such as genetic diseases and developmental problems. A genetic analysis was performed on the sperm from exposed mice alongside non-exposed controls. The results showed that mice exposed to second-hand smoke had higher rates of mutation in their sperm. These effects were measured at exposure levels that are comparable to those encountered by humans in proximity to smokers. In addition, the study found that sperm DNA may be particularly sensitive to the effects of smoke, relative to other cells in the body. The results of this study suggest that exposure to second-hand smoke is harmful to sperm and may have effects on reproduction. This study was published in Proceedings of the National Academy of Sciences USA (2011 Aug 2), 108(31):12811-12814.

Genetic Toxicology and Toxicogenomic Analysis of Three Cigarette Smoke Condensates In Vitro Reveals Few Differences Among Full-Flavor, Blonde, and Light Products

Cigarette smoking leads to a number of detrimental health outcomes and Health Canada is responsible for regulating tobacco products in an effort to reduce or prevent the negative health impacts associated with smoking. Some tobacco companies produce different brands of cigarettes that are marketed as reduced harm tobacco products. Early versions of such products included those marketed as “light” cigarettes, which differed from regular cigarettes due to filter ventilation and/or differences in chemical constituents. In order to establish baseline similarities and differences among different tobacco brands available in Canada, Health Canada conducted the present study to examine the toxicity of cigarette smoke condensate (CSC), particles and chemicals collected on a filter that are emitted from the end of the cigarette that the smoker inhales, from three tobacco products, encompassing a full-flavour, blonde, and a product previously marketed as “light”. The results indicated that the three products induced similar levels of DNA damage and toxicity in both bacterial assays and in mouse cells in culture. The study also explored the changes in expression of all the genes within the cells, which can indicate the biological functions that are affected by exposure. Each brand yielded very similar profiles within each time point and concentration. This work establishes baseline CSC toxicity profiles that Health Canada will use as a point of reference for comparison with data generated for novel tobacco products marketed as reduced harm or modified risk. This study was published in Environmental and Molecular Mutagenesis (2012 May), 53(4):281-296.

The Analysis of Mainstream Smoke Emissions Of Canadian ‘Super Slim’ Cigarettes

The super slim cigarette is a relatively new type of cigarette in Canada and features a significantly smaller diameter compared to all other cigarettes sold in the Canadian market.  Information on how the super slim design impacts mainstream smoke emissions is limited, and consumers may be misled into believing that the super slim cigarette produces lower toxic emissions and is therefore a ‘less harmful’ cigarette. As part of its mandate, Health Canada helps to educate the public about the health risks associated with tobacco. In this study, the smoke machine yields of select toxic chemicals in the mainstream smoke of the super slim cigarettes were compared with those from other Canadian cigarettes.  Although the super slim cigarettes contain approximately half the amount of tobacco of other Canadian cigarettes, the yields of selected toxic chemicals were not systematically reduced. Some chemicals, such as formaldehyde and phenols, were significantly increased as a result of the super slim design. For the super slim cigarettes containing a mixed tobacco blend, there was also a significant increase in the yields of the tobacco-specific nitrosamines, which are chemicals specific to tobacco and classified as carcinogens. Notably, the super slim cigarette yielded similar amounts of nicotine as the other Canadian cigarettes. Overall, there are no changes in emission levels that have been shown to reduce exposure or risk in a way that is meaningful and the super slim cigarette should not be considered a ‘less harmful’ cigarette. Health Canada will use the results of this study to inform risks assessments on the hazards and health risks posed by tobacco products. The results of this study are published in the journal Tobacco Control (E Pub on July 20, 2012).

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