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Introduction
Cell exposure to exogenous genotoxic agents, such as non-ionizing and ionizing radiations, oxidative stress and chemical mutagens causes a variety of DNA damages, resulting in genomic alterations [1]. To reduce genomic instability, cells have DNA damage responses (DDR) and DNA repair proteins to remove these lesions [[2], [3], [4]].
Reactive oxygen species (ROS) comprise products from the oxidative metabolism involved in modulation of cell survival, differentiation and cell signaling, when at appropriate concentrations [5]. However, at high levels, ROS cause lipid, protein and DNA damages, contributing to genomic instability [6]. Repair of oxidative DNA damages occurs by base excision repair (BER) and nucleotide excision repair (NER) pathways, which contribute to genomic stabilization [7] (Fig. 1).
Protection of non-oxidative DNA damage can occur through mechanisms known as checkpoints. During this process, proteins recognize DNA damages and cell division is arrested until DNA repair is complete [8]. Tp53 (tumor protein 53) gene product (p53 protein) is a protein activated by ATM (ataxia telangiectasia mutated) protein playing a key role in checkpoints, responsible for stopping cell cycle activity to allow activation of repair pathways, functioning as a mediator, transducer, and indirect effector [9,10]. Tp53 mutations are frequent in tobacco-related cancers [11].
Telomere is a region of repetitive nucleotide sequences at the end of each eukaryotic chromosome, protecting them from attrition and damages [12]. Dysfunctional telomeres are also known as DNA damages and activate DDR pathways, such as Tp53 [13]. Telomere shortening, which could be induced by prolonged oxidative stress, acts in aging by ATM and Tp53 products. These proteins are involved in telomere-induced apoptosis and cellular senescence [9].
Low power lasers (LPL), power ranging 1 up to 1000 mW and typical exposure time between few seconds and few minutes, emit radiations that are considered safe and also non-ionizing, being because these features potential used in therapeutic protocols for treatment of pain, wound healing and various diseases [14]. In fact, at high powers, lasers cause DNA damage [15,16] and deletion of chromosome [17].
Despite clinical applications, LPL underlying biochemical mechanisms remain poorly understood yet, so that their use is largely empirical and based on professional practice. This justifies studies aiming to identify and describe cell signalizing pathways trigged or modified by LPL, as well as, their effects on gene expression, including those related to genome stability. Also, laser irradiation parameters, such as wavelength, coherence, fluence (dose), emission mode (pulsed or continuous wave), polarization, timing and spot size are not yet optimized. The efficacy of therapies based on LPL depends on the correct choice of these parameters and biphasic LPL-induced therapeutic effects have been reported [[18], [19], [20]]. In fact, deviation from optimal parameter choice may result in reduced effectiveness of the treatment, or even negative results. In addition, systemic effects are yet to be explored, although some applications seem be promising, such as wound repair improvement [21], glycemia reduction by laser irradiation of salivary glands [22], exercise capability and muscle performance improvement [23], life span prolongation of gamma-irradiated rats [24] and blood pressure reduction in spontaneous hypertensive rats [25].
Recent studies have suggested that photobiostimulatory effect of these lasers could influence the genomic stabilization [26] which occurs as LPL radiations could induce lesions in the DNA at sub-lethal levels, which in turn could induce DNA repair mechanisms [27]. Another study suggested that LPL could also influence telomere stabilization by modulation of mRNA expression from genes related to telomere stabilization, such as TRF1 and TRF2 [28].
As genomic stability plays a key role in cell homeostasis, therefore, for LPL-induced photobiostimulation, comprehension of effects on DNA repair and telomere stabilization can help understanding the mechanism involved in lasertherapy from a molecular biology point of view. Thus, this review focuses on genomic stabilization and telomere maintenance as possible targets to improve therapeutic protocols based on low power lasers.
