Exposure of mice to cigarette smoke and/or light causes DNA alterations in heart and aorta

Department of Health Sciences, University of Genoa, Genoa, Italy.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis (Impact Factor: 3.68). 09/2008; 644(1-2):38-42. DOI: 10.1016/j.mrfmmm.2008.06.012
Source: PubMed


Cigarette smoke (CS) is a major risk factor for cardiovascular diseases, cancer, and other chronic degenerative diseases. UV-containing light is the most ubiquitous DNA-damaging agent existing in nature, but its possible role in cardiovascular diseases had never been suspected before, although it is known that mortality for cardiovascular diseases is increased during periods with high temperature and solar irradiation. We evaluated whether exposure of Swiss CD-1 mice to environmental CS (ECS) and UV-C-covered halogen quartz lamps, either individually or in combination, can cause DNA damage in heart and aorta cells. Nucleotide alterations were evaluated by (32)P postlabeling methods and by HPLC-electrochemical detection. The whole-body exposure of mice to ECS considerably increased the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and of bulky DNA adducts in both heart and aorta. Surprisingly, even exposure to a light that simulated solar irradiation induced oxidatively generated damage in both tissues. The genotoxic effects of UV light in internal organs is tentatively amenable to formation of unidentified long-lived mutagenic products in the skin of irradiated mice. Nucleotide alterations were even more pronounced when the mice were exposed to smoke and/or light during the first 5 weeks of life rather than during adulthood for an equivalent period of time. Although the pathogenetic meaning is uncertain, DNA damage in heart and aorta may tentatively be related to cardiomyopathies and to the atherogenesis process, respectively.

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    • "Indeed UV exposure doubled oxidative DNA damage levels in the aorta of mice exposed to UV-light 6 h per day for 5 weeks (Izzotti et al., 2008). The genotoxic effects of UV light in internal organs is tentatively amenable to formation of unidentified long-lived mutagenic products in the skin of irradiated mice. "
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    ABSTRACT: Atherosclerosis is associated with DNA damage in both circulating and vessel-wall cells and DNA adducts derived from exposure to environmental mutagens are abundant in atherosclerotic vessels. Environmental chemical carcinogens identified as risk factor for atherosclerosis include polycyclic aromatic hydrocarbons (benzo(a)pyrene, dimethylbenz(a)anthracene, beta-naphthoflavone, pyrene, 3-methylcolanthrene), arsenic, cadmium, 1,3-butadiene, cigarette smoke. Accordingly, polymorphisms of genes encoding for phase I/II metabolic reaction and DNA repair are risk factor for cardiovascular diseases, although their role is negligible as compared to other risk factors. The pathogenic relevance of mutation-related molecular damage in atherosclerosis has been demonstrated in experimental animal models involving the exposure to chemical mutagens. The relevance of mutation-related events in worsening atherosclerosis prognosis has been demonstrated in human clinical studies mainly as referred to mitochondrial DNA damage. Atherosclerosis is characterized by the occurrence of high level of oxidative damage in blood vessel resulting from both endogenous and exogenous sources. Mitochondrial damage is a main endogenous source of oxidative stress whose accumulation causes activation of intrinsic apoptosis through BIRC2 inhibition and cell loss contributing to plaque development and instability. Environmental physical mutagens, including ionizing radiation, are a risk factor for atherosclerosis even at the low exposure dose occurring in case of occupational exposure or the high exposure doses occurring during radiotherapy. Conversely, the role of exciting UV radiation in atherosclerosis is still uncertain. This review summarizes the experimental and clinical evidence supporting the pathogenic role of mutation-related pathway in atherosclerosis examining the underlying molecular mechanisms. Copyright © 2015 Elsevier GmbH. All rights reserved.
    International Journal of Hygiene and Environmental Health 02/2015; 218(3). DOI:10.1016/j.ijheh.2015.01.007 · 3.83 Impact Factor
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    • "The acute adverse effects of smoking on myocardial relaxation were originally observed in coronary artery disease patients [14], with acute impairment of coronary vasomotion implicated as the main cause [15]. Such effects on diastolic function are also detected in healthy smokers [5-7] Cigarette smoke contains significant amounts of free radicals, promoting oxidative stress and inflammation [16] At the cellular level, decreased function of myocardial mitochondria [17] and DNA damage [18] has been observed. These mechanisms may be implicated in delaying myocardial relaxation from acute use and promoting atherosclerosis and cardiovascular disease from chronic use. "
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    ABSTRACT: Electronic cigarettes have been developed and marketed in recent years as smoking substitutes. However, no studies have evaluated their effects on the cardiovascular system. The purpose of this study was to examine the immediate effects of electronic cigarette use on left ventricular (LV) function, compared to the well-documented acute adverse effects of smoking. Echocardiographic examinations were performed in 36 healthy heavy smokers (SM, age 36 ± 5 years) before and after smoking 1 cigarette and in 40 electronic cigarette users (ECIG, age 35 ± 5 years) before and after using the device with “medium-strength” nicotine concentration (11 mg/ml) for 7 minutes. Mitral flow diastolic velocities (E, A), their ratio (E/A), deceleration time (DT), isovolumetric relaxation time (IVRT) and corrected-to-heart rate IVRT (IVRTc) were measured. Mitral annulus systolic (Sm), and diastolic (Em, Am) velocities were estimated. Myocardial performance index was calculated from Doppler flow (MPI) and tissue Doppler (MPIt). Longitudinal deformation measurements of global strain (GS), systolic (SRs) and diastolic (SRe, SRa) strain rate were also performed. Baseline measurements were similar in both groups. In SM, IVRT and IVRTc were prolonged, Em and SRe were decreased, and both MPI and MPIt were elevated after smoking. In ECIG, no differences were observed after device use. Comparing after-use measurements, ECIG had higher Em (P = 0.032) and SRe (P = 0.022), and lower IVRTc (P = 0.011), MPI (P = 0.001) and MPIt (P = 0.019). The observed differences were significant even after adjusting for changes in heart rate and blood pressure. Although acute smoking causes a delay in myocardial relaxation, electronic cigarette use has no immediate effects. Electronic cigarettes’ role in tobacco harm reduction should be studied intensively in order to determine whether switching to electronic cigarette use may have long-term beneficial effects on smokers’ health. Trial registration Current Controlled Trials ISRCTN16974547
    BMC Cardiovascular Disorders 06/2014; 14(1):78. DOI:10.1186/1471-2261-14-78 · 1.88 Impact Factor
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    • "The effects of light on mouse lung were confirmed by multigene expression analysis (Izzotti et al. 2004). Furthermore, exposure to light of albino mice, especially early in life, induced oxidatively generated DNA damage even in heart and aorta (Izzotti et al. 2008). Epidemiological studies have suggested an association between exposure to solar UV radiation and occurrence of lymphoid malignancies, whose incidence has substantially increased worldwide during the last decades. "
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    ABSTRACT: The light delivered by artificial illumination systems, and in particular by halogen quartz bulbs, contains UVA, UVB, and UVC radiation, is genotoxic to both bacterial and human cells and is potently carcinogenic to hairless mice. Since IARC has classified UV radiation in Group 1, any source of UV light poses a carcinogenic hazard to humans. Suitable regulations would be needed in order to control the safety of the light emitted by artificial light sources.
    Archives of Toxicology 02/2013; 87(3). DOI:10.1007/s00204-013-1015-7 · 5.98 Impact Factor
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