The development of cancer in humans and animals is a multistep process. The complex series of cellular and molecular changes participating in cancer development are mediated by a diversity of endogenous and exogenous stimuli. One type of endogenous damage is that arising from intermediates of oxygen (dioxygen) reduction - oxygen-free radicals (OFR), which attacks not only the bases but also the deoxyribosyl backbone of DNA. Thanks to improvements in analytical techniques, a major achievement in the understanding of carcinogenesis in the past two decades has been the identification and quantification of various adducts of OFR with DNA. OFR are also known to attack other cellular components such as lipids, leaving behind reactive species that in turn can couple to DNA bases. Endogenous DNA lesions are genotoxic and induce mutations. The most extensively studied lesion is the formation of 8-OH-dG. This lesion is important because it is relatively easily formed and is mutagenic and therefore is a potential biomarker of carcinogenesis. Mutations that may arise from formation of 8-OH-dG involve GC --> TA transversions. In view of these findings, OFR are considered as an important class of carcinogens. The effect of OFR is balanced by the antioxidant action of non-enzymatic antioxidants as well as antioxidant enzymes. Non-enzymatic antioxidants involve vitamin C, vitamin E, carotenoids (CAR), selenium and others. However, under certain conditions, some antioxidants can also exhibit a pro-oxidant mechanism of action. For example, beta-carotene at high concentration and with increased partial pressure of dioxygen is known to behave as a pro-oxidant. Some concerns have also been raised over the potentially deleterious transition metal ion-mediated (iron, copper) pro-oxidant effect of vitamin C. Clinical studies mapping the effect of preventive antioxidants have shown surprisingly little or no effect on cancer incidence. The epidemiological trials together with in vitro experiments suggest that the optimal approach is to reduce endogenous and exogenous sources of oxidative stress, rather than increase intake of anti-oxidants. In this review, we highlight some major achievements in the study of DNA damage caused by OFR and the role in carcinogenesis played by oxidatively damaged DNA. The protective effect of antioxidants against free radicals is also discussed.
Arsenic (As) is a toxic metalloid element that is present in air, water and soil. Inorganic arsenic tends to be more toxic than organic arsenic. Examples of methylated organic arsenicals include monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)]. Reactive oxygen species (ROS)-mediated oxidative damage is a common denominator in arsenic pathogenesis. In addition, arsenic induces morphological changes in the integrity of mitochondria. Cascade mechanisms of free radical formation derived from the superoxide radical, combined with glutathione-depleting agents, increase the sensitivity of cells to arsenic toxicity. When both humans and animals are exposed to arsenic, they experience an increased formation of ROS/RNS, including peroxyl radicals (ROO•), the superoxide radical, singlet oxygen, hydroxyl radical (OH•) via the Fenton reaction, hydrogen peroxide, the dimethylarsenic radical, the dimethylarsenic peroxyl radical and/or oxidant-induced DNA damage. Arsenic induces the formation of oxidized lipids which in turn generate several bioactive molecules (ROS, peroxides and isoprostanes), of which aldehydes [malondialdehyde (MDA) and 4-hydroxy-nonenal (HNE)] are the major end products. This review discusses aspects of chronic and acute exposures of arsenic in the etiology of cancer, cardiovascular disease (hypertension and atherosclerosis), neurological disorders, gastrointestinal disturbances, liver disease and renal disease, reproductive health effects, dermal changes and other health disorders. The role of antioxidant defence systems against arsenic toxicity is also discussed. Consideration is given to the role of vitamin C (ascorbic acid), vitamin E (α-tocopherol), curcumin, glutathione and antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase in their protective roles against arsenic-induced oxidative stress.
Transition metal ions are key elements of various biological processes ranging from oxygen formation to hypoxia sensing, and therefore, their homeostasis is maintained within strict limits through tightly regulated mechanisms of uptake, storage and secretion. The breakdown of metal ion homeostasis can lead to an uncontrolled formation of reactive oxygen species, ROS (via the Fenton reaction, which produces hydroxyl radicals), and reactive nitrogen species, RNS, which may cause oxidative damage to biological macromolecules such as DNA, proteins and lipids. An imbalance between the formation of free radicals and their elimination by antioxidant defense systems is termed oxidative stress. Most vulnerable to free radical attack is the cell membrane which may undergo enhanced lipid peroxidation, finally producing mutagenic and carcinogenic malondialdehyde and 4-hydroxynonenal and other exocyclic DNA adducts. While redox-active iron (Fe) and copper (Cu) undergo redox-cycling reactions, for a second group of redox-inactive metals such as arsenic (As) and cadmium (Cd), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. While arsenic is known to bind directly to critical thiols, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. Redox-inert zinc (Zn) is the most abundant metal in the brain and an essential component of numerous proteins involved in biological defense mechanisms against oxidative stress. The depletion of zinc may enhance DNA damage by impairing DNA repair mechanisms. Intoxication of an organism by arsenic and cadmium may lead to metabolic disturbances of redox-active copper and iron, with the occurrence of oxidative stress induced by the enhanced formation of ROS/RNS. Oxidative stress occurs when excessive formation of ROS overwhelms the antioxidant defense system, as is maintained by antioxidants such as ascorbic acid, alpha-tocopherol, glutathione (GSH), carotenoids, flavonoids and antioxidant enzymes which include SOD, catalase and glutathione peroxidase. This review summarizes current views regarding the role of redox-active/inactive metal-induced formation of ROS, and modifications to biomolecules in human disease such as cancer, cardiovascular disease, metabolic disease, Alzheimer's disease, Parkinson's disease, renal disease, blood disorders and other disease. The involvement of metals in DNA repair mechanisms, tumor suppressor functions and interference with signal transduction pathways are also discussed.
A review is presented of the manufacture and use of different types of plastic, and the effects of pollution by these materials on animal, human and environmental health, insofar as this is known. Since 2004, the world has made as much plastic as it did in the previous half century, and it has been reckoned that the total mass of virgin plastics ever made amounts to 8.3 billion tonnes, mainly derived from natural gas and crude oil, used as chemical feedstocks and fuel sources. Between 1950 and 2015, a total of 6.3 billion tonnes of primary and secondary (recycled) plastic waste was generated, of which around 9% has been recycled, and 12% incinerated, with the remaining 79% either being stored in landfills or having been released directly into the natural environment. In 2015, 407 million tonnes (Mt) of plastic was produced, of which 164 Mt was consumed by packaging (36% of the total). Although quoted values vary, packaging probably accounts for around one third of all plastics used, of which approximately 40% goes to landfill, while 32% escapes the collection system. It has been deduced that around 9 Mt of plastic entered the oceans in 2010, as a result of mismanaged waste, along with up to 0.5 Mt each of microplastics from washing synthetic textiles, and from the abrasion of tyres on road surfaces. However, the amount of plastics actually measured in the oceans represents less than 1% of the (at least) 150 Mt reckoned to have been released into the oceans over time. Plastic accounts for around 10% by mass of municipal waste, but up to 85% of marine debris items - most of which arrive from land-based sources. Geographically, the five heaviest plastic polluters are P. R. China, Indonesia, Philippines, Vietnam and Sri Lanka, which between them contribute 56% of global plastic waste. Larger, primary plastic items can undergo progressive fragmentation to yield a greater number of increasingly smaller 'secondary' microplastic particles, thus increasing the overall surface area of the plastic material, which enhances its ability to absorb, and concentrate, persistent organic pollutants (POPs) such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs), with the potential to transfer them to the tissues of animals that ingest the microplastic particles, particularly in marine environments. Although fears that such microparticles and their toxins may be passed food webs to humans are not as yet substantiated, the direct ingestion of microplastics by humans drinking water is a distinct possibility - since 92% of samples taken in the USA and 72% in Europe showed their presence - although any consequent health effects are as yet unclear. Foodstuffs may also become contaminated by microplastics from the air, although any consequent health effects are also unknown. In regard to such airborne sources, it is noteworthy that small plastic particles have been found in human lung tissue, which might prove an adverse health issue under given circumstances. It is also very striking that microplastics have been...
A review is made of the current state of agriculture, emphasising issues of soil erosion and dependence on fossil fuels, in regard to achieving food security for a relentlessly enlarging global population. Soil has been described as "the fragile, living skin of the Earth", and yet both its aliveness and fragility have all too often been ignored in the expansion of agriculture across the face of the globe. Since it is a pivotal component in a global nexus of soil-water-air-energy, how we treat the soil can impact massively on climate change - with either beneficial or detrimental consequences, depending on whether the soil is preserved or degraded. Regenerative agriculture has at its core the intention to improve the health of soil or to restore highly degraded soil, which symbiotically enhances the quality of water, vegetation and land-productivity. By using methods of regenerative agriculture, it is possible not only to increase the amount of soil organic carbon (SOC) in existing soils, but to build new soil. This has the effect of drawing down carbon from the atmosphere, while simultaneously improving soil structure and soil health, soil fertility and crop yields, water retention and aquifer recharge - thus ameliorating both flooding and drought, and also the erosion of further soil, since runoff is reduced. Since food production on a more local scale is found to preserve the soil and its quality, urban food production should be seen as a significant potential contributor to regenerative agriculture in the future, so long as the methods employed are themselves 'regenerative'. If localisation is to become a dominant strategy for dealing with a vastly reduced use of fossil fuels, and preserving soil quality - with increased food production in towns and cities - it will be necessary to incorporate integrated ('systems') design approaches such as permaculture and the circular economy (which minimise and repurpose 'waste') within the existing urban infrastructure. In addition to growing food in urban space, such actions as draught-proofing and thermally insulating existing building stock, and living/ working on a more local scale, would serve well to cut our overall energy consumption. In order to curb our use of fossil fuels, methods for reducing overall energy use must be considered at least equally important to expanding low-carbon energy production. In synopsis, it is clear that only by moving from the current linear, 'take, make, dispose (waste-creation)' model for resource-consumption, to the systemic, circular alternative of 'reduce, reuse, recycle, regenerate', are we likely to meet demands for future generations.
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