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
Saturday, May 9, 2026
Dulcolax: Brand Name Medication Guide For Constipation And Bowel Health
Dulcolax is the brand name for bisacodyl, a medication used in the management of conditions associated with constipation and bowel health. Brand name medications are pharmaceutical products marketed under a proprietary name by the company that originally developed them. Understanding the relationship between brand name and generic formulations, as well as the conditions for which the medication is approved, helps patients make informed choices about their treatment. Laxatives are classified by their mechanism of action. Bulk-forming laxatives add fiber to stool, increasing its water content and bulk. Osmotic laxatives draw water into the intestine by osmosis, softening stool and stimulating movement. Stimulant laxatives directly stimulate the muscles of the intestinal wall to contract and move stool along. Stool softeners add moisture to stool surface without stimulating bowel movement. Most physicians recommend starting with dietary and lifestyle modifications before resorting to laxatives for routine constipation. The brand name Dulcolax has built a clinical track record through use in a wide range of patients and healthcare settings. Brand versions and their generic equivalents contain the same active ingredient at the same strength, but may differ in inactive ingredients such as fillers, binders, and coatings. In most cases, generic formulations are therapeutically equivalent and offer cost savings, though some patients prefer to stay on a specific formulation for consistency. When prescribed Dulcolax, patients should follow the guidance of their prescribing physician regarding dose, frequency, and duration of therapy. The medication should be stored as directed on the label, typically at room temperature away from heat and moisture. Any unused medication should not be disposed of by flushing down the drain unless the label specifically says to do so, as this can harm the environment. Comprehensive details on Dulcolax and other medications used for constipation and bowel health are available through constipation and bowel health. This resource provides evidence-based summaries to help patients and healthcare providers stay informed about treatment options in this therapeutic area.
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