Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer

Abstract

Smoking is a major risk factor for a variety of diseases, including cancer and immune-mediated inflammatory diseases. Tobacco smoke contains a mixture of chemicals, including a host of reactive oxygen-and nitrogen species (ROS and RNS), among others, that can damage cellular and sub-cellular targets, such as lipids, proteins, and nucleic acids. A growing body of evidence supports a key role for smoking-induced ROS and the resulting oxidative stress in inflammation and carcinogenesis. This comprehensive and up-to-date review covers four interrelated topics, including 'smoking', 'oxidative stress', 'inflammation', and 'cancer'. The review discusses each of the four topics, while exploring the intersections among the topics by highlighting the macromolecular damage attributable to ROS. Specifically, oxidative damage to macromolecular targets, such as lipid peroxidation, post-translational modification of proteins, and DNA adduction, as well as enzymatic and non-enzymatic antioxidant defense mechanisms, and the multi-faceted repair pathways of oxidized lesions are described. Also discussed are the biological consequences of oxidative damage to macromolecules if they evade the defense mechanisms and/or are not repaired properly or in time. Emphasis is placed on the genetic-and epigenetic alterations that may lead to transcriptional deregulation of functionally-important genes and disruption of regulatory elements. Smoking-associated oxidative stress also activates the inflammatory response pathway, which triggers a cascade of events of which ROS production is an initial yet indispensable step. The release of ROS at the site of damage and inflammation helps combat foreign pathogens and restores the injured tissue, while simultaneously increasing the burden of oxidative stress. This creates a vicious cycle in which smoking-related oxidative stress causes inflammation, which in turn, results in further generation of ROS, and potentially increased oxidative damage to macromolecular targets that may lead to cancer initiation and/or progression.

Hydroxychloroquine induces oxidative DNA damage and mutation in mammalian cells

“…Similarly, we have quantified cII mutant frequency, as an indicator of the mutagenic potency of HCQ in vitro. Although 8-oxodG predominantly induces G:C→T:A transversion, in addition to G:C→A:T transition and G:C→C:G transversion [36], other types of DNA damage, potentially induced by HCQ but not measured in this study, may also have similar mutational signature [38,47,48]. Thus, we have not attributed (explicitly or implicitly) the increased relative cII mutant frequency in HCQ-treated cells directly to 8-oxodG because other types of damage (not measured in this study) may also be produced by HCQ treatment.…”

“…While investigations of the mechanisms of action of HCQ have mainly centered on its intracellular effects, specifically on lysosomal function and activity [19,21,24], very little is known about the interaction of HCQ with DNA, including its DNA damaging-and mutagenic potentials [30]. This is an important gap in knowledge considering that HCQ can produce reactive oxygen species (ROS) [31][32][33][34][35] that are known to cause DNA damage and mutation [36]. The present study is the first investigation of the genotoxicity of HCQ whereby both the DNA damaging-and mutagenic effects of this drug are tested in mammalian cells, at concentrations that are comparable to clinically achievable doses in patient populations.…”

The Adverse Impact of Incense Smoke on Human Health: From Mechanisms to Implications

“…Notably, tobacco smoking has been also well recognized an oxidative stressor that induces the accumulation of reactive oxygen species, which in turn leads to damages to the body. 142 Since both incense smoke and tobacco smoke may affect the biological systems through the same pathway, it would not be surprising that the effects of incense smoke in ever or current smokers are different from those in never smokers, but in varying ways. For instance, more pronounced association between incense use and lung cancer in male smokers was documented in the literature.…”

The Key Differences between Human Papillomavirus-Positive and -Negative Head and Neck Cancers: Biological and Clinical Implications

“…However, the combination of alcohol and tobacco has a multiplicative associated risk [30]. Studies have shown that the reactive oxygen and nitrogen species found in cigarette smoke (CS) are known to lead to oxidative stress and activation of proinflammatory pathways in lung fibroblasts [31][32][33]. Recently, it was shown that fibroblasts exposed to CS have the potential to alter the tumor microenvironment (TME) in HNSCC through similar mechanisms as the lung fibroblasts [34,35].…”