Endogenous DNA damage in humans: a review of quantitative data
By academic.oup.com
DNA damage plays a major role in mutagenesis, carcinogenesis and ageing. The chemical events that lead to DNA damage include hydrolysis, exposure to reactive oxygen substances (ROS) and other reactive metabolites. These reactions are triggered by exposure to exogenous chemicals or they can result from metabolic, endogenous processes. The concentrations and mutagenic potentials of known carcinogens to which we are exposed in our environment are insufficient to explain the high incidence of sporadic cancer that is actually seen in our population (Epe, 2002). Innate factors can also not suffice to explain this high incidence. Epidemiology shows that, in developed societies, exogenous factors are a necessary condition in about 75–80% of cancer cases (Doll and Peto, 1981; Trichopoulos et al., 1994). So, mutations due to DNA damage, caused by unidentified exogenous agents, and to an increase in endogenous damage modulated by exogenous factors must play a role in most cases of cancer, in addition to changes in gene expression due to exogenous conditions. A thorough knowledge of the types and prevalence of endogenous DNA damage can be considered essential for an understanding of the interaction of exogenous agents and influences with endogenous processes in the induction of cancer and other diseases. In particular, this is important for risk analysis concerning low dose environmental factors. Endogenous DNA damage occurs at a high frequency compared with exogenous damage and the types of damage produced by normal cellular processes are identical or very similar to those caused by some environmental agents (Jackson and Loeb, 2001). The study of endogenous damage is also of importance to chemoprevention. It is evident that if an approach could be developed leading to a decrease in endogenous DNA damage and endogenous mutations, the incidence of cancer and other diseases might be substantially reduced, even without a reduction in exogenous mutations.
Oxidative DNA damage
In living cells ROS are formed continuously as a consequence of metabolic and other biochemical reactions as well as external factors. These ROS include superoxide (O2–·), hydrogen peroxide (H2O2), hydroxyl radicals (OH·) and singlet oxygen (1O2) and they can oxidize DNA, which can lead to several types of DNA damage, including oxidized bases and single‐ and double‐strand breaks. DNA damage produced by ROS is the most frequently occurring damage.
Oxidatively modified DNA is, despite extensive DNA repair, abundant in many human tissues, especially in tumours (Iida et al., 2001; Li et al., 2002). Many defence mechanisms within the organism have evolved to limit the levels of reactive oxidants and the damage they induce (Slupphaug et al., 2003). Oxidative stress occurs when the production of ROS exceeds the body’s natural antioxidant defence mechanisms, causing damage to macromolecules such as DNA, proteins and lipids. ROS also inactivate antioxidant enzymes (Kono and Fidovich, 1982; Tabatabaie and Floyd, 1994). So, as pointed out by Epe (2002), any change in the endogenous generation of ROS or cellular antioxidants or in the efficiency of DNA repair should cause a corresponding modulation of the steady‐state levels of oxidative DNA modifications, which in turn should modulate the mutation rate and ultimately the cancer incidence. Epidemiological evidence from different studies points to reduced risks for cancer, particularly in the upper gastrointestinal tract and airways, associated with a diet rich in antioxidants and/or a high content of antioxidants in plasma samples (Loft and Poulsen, 1996).
Data suggest that the rate of damage decreases with age, possibly along with the decreasing rate of metabolism, whereas the steady‐state levels increase due to failing repair (Loft and Poulsen, 1996).
Source: https://academic.oup.com/mutage/article/doi/10.1093/mutage/geh025/1482185/Endogenous-DNA-damage-in-humans-a-review-of
Wednesday, May 13, 2026
Oxcarbazepine: The Generic Form Of Trileptal Explained
Oxcarbazepine is the generic name of the medication sold under the brand name Trileptal. Generic medications contain the same active ingredient at the same dose and strength as their brand name counterparts and must meet the same FDA standards for quality, purity, and bioequivalence. The development and approval of generic drugs play an important role in making effective treatments more accessible and affordable for patients. Approximately 70 percent of people with epilepsy achieve adequate seizure control with antiepileptic medication. For those with drug-resistant epilepsy, newer medications, dietary therapies such as the ketogenic diet, and surgical options may be considered. Antiepileptic medications are also used outside of epilepsy for conditions including chronic pain, migraine prevention, bipolar disorder, and anxiety, reflecting the broad relevance of neuronal excitability regulation to numerous medical conditions. The pharmacological action of oxcarbazepine is the basis for its use in treating conditions within the category of seizure and epilepsy treatment. Understanding the mechanism by which the active compound produces its therapeutic effects helps patients appreciate why the medication needs to be taken consistently and at the correct dose to achieve the best results. Switching between brand name and generic versions of a medication is generally considered safe when the products are bioequivalent, but patients should inform their doctor if they notice any differences in effect after a formulary change. Some patients with conditions requiring precise drug levels in the blood may be monitored more closely during transitions. For most patients, however, approved generics provide equivalent therapeutic benefit to the brand name product. The seizure and epilepsy treatment section on seizure and epilepsy treatment covers both brand name and generic treatment options, giving patients a complete picture of what is available. Cost, insurance coverage, and pharmacy availability are practical factors to discuss with a pharmacist when filling a prescription for oxcarbazepine.
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