Telomere shortening and DNA damage of embryonic stem cells induced by cigarette smoke

Stem Cell and Functional Genomics Laboratory, Department of Biochemistry, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China
Reproductive Toxicology (Impact Factor: 3.23). 07/2012; 35(1). DOI: 10.1016/j.reprotox.2012.07.003
Source: PubMed


Embryonic stem cells (ESCs) provide a valuable in vitro model for testing toxicity of chemicals and environmental contaminants including cigarette smoke. Mouse ESCs were acutely or chronically exposed to smoke components, cigarette smoke condensate (CSC), or cadmium, an abundant component of CSC, and then evaluated for their self-renewal, apoptosis, DNA damage and telomere function. Acute exposure of ESCs to high dose of CSC or cadmium increased DNA damage and apoptosis. Yet, ESCs exhibited a remarkable capacity to recover following absence of exposure. Chronic exposure of ESCs to low dose of CSC or cadmium resulted in shorter telomeres and DNA damage. Together, acute exposure of ESCs to CSC or cadmium causes immediate cell death and reduces pluripotency, while chronic exposure of ESCs to CSC or cadmium leads to DNA damage and telomere shortening. Notably, a sub-proportion of ESCs during passages is selected to resist to smoke-induced oxidative damage to telomeres.

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    • "Current research suggests that cigarette smoke is a powerful environmental modifier of DNAm (reviewed in (Lee and Pausova 2013)). Cigarette smoke contains a large number of chemicals, such as carcinogens, nicotine and carbon monoxide, that have been shown to modify DNAm in differentiating and dividing cells (Cuozzo et al. 2007; Di et al. 2012; Han et al. 2001; Huang et al. 2012; Mercer et al. 2009; Mortusewicz et al. 2005; Satta et al. 2008; Shahrzad et al. 2007). "
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    ABSTRACT: DNA methylation is the most studied epigenetic modification, capable of controlling gene expression in the contexts of normal traits or diseases. It is highly dynamic during early embryogenesis and remains relatively stable throughout life, and such patterns are intricately related to human development. DNA methylation is a quantitative trait determined by a complex interplay of genetic and environmental factors. Genetic variants at a specific locus can influence both regional and distant DNA methylation. The environment can have varying effects on DNA methylation depending on when the exposure occurs, such as during prenatal life or during adulthood. In particular, cigarette smoking in the context of both current smoking and prenatal exposure is a strong modifier of DNA methylation. Epigenome-wide association studies have uncovered candidate genes associated with cigarette smoking that have biologically relevant functions in the etiology of smoking-related diseases. As such, DNA methylation is a potential mechanistic link between current smoking and cancer, as well as prenatal cigarette-smoke exposure and the development of adult chronic diseases.
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