A majority of potential radioprotective synthetic compounds have demonstrated limited clinical application owing to their inherent toxicity, and thus, the seeking of naturally occurring herbal products, such as ginseng, for their radioprotective capability has become an attractive alternative. In general, ginseng refers to the roots of the species of the genus Panax. As a medicinal herb, ginseng has been widely used in traditional Chinese medicine for its wide spectrum of medicinal effects, such as tonic, immunomodulatory, antimutagenic, adaptogenic and antiaging activities. Many of its medicinal effects are attributed to the triterpene glycosides known as ginsenosides (saponins). This review addresses the issue of the radioprotective effects of ginseng on mammalian cells both in vitro and in vivo. Results indicate that the water-soluble extract of whole ginseng appears to give a better protection against radiation-induced DNA damage than does the isolated ginsenoside fractions. Since free radicals play an important role in radiation-induced damage, the underlying radioprotective mechanism of ginseng could be linked, either directly or indirectly, to its antioxidative capability by the scavenging free radicals responsible for DNA damage. In addition, ginseng's radioprotective potential may also be related to its immunomodulating capabilities. Ginseng is a natural product with worldwide distribution, and in addition to its antitumor properties, ginseng appears to be a promising radioprotector for therapeutic or preventive protocols capable of attenuating the deleterious effects of radiation on human normal tissue, especially for cancer patients undergoing radiotherapy.
Only two radioprotective compounds, amifostine and palifermin, currently have the US FDA approval for use in radiation therapy. However, several agents have been reported that show therapeutic promise. Many of these agents are free radical scavengers/antioxidants. Superoxide dismutase and superoxide dismutase mimetics, nitroxides and dietary antioxidants are all being investigated. Recently, alternative strategies of drug development have been evolving, which focus on targeting the series of cellular insult recognition/repair responses initiated following radiation. These agents, which include cytokines/growth factors, angiotensin-converting enzyme inhibitors and apoptotic modulators, show promise of having significant impact on the mitigation of radiation injury. Herein, we review current literature on the development of radioprotectors with emphasis on compounds with proven or potential usefulness in radiation therapy.
Melanoma is the most lethal of all cutaneous malignancies and additional treatment paradigms are needed. We explored the activity of PDT on human A-375 melanoma cells in vitro with different light wavelengths using porphyrin photosensitizers. The effect of red, green, and blue light in the cytotoxicity of these cells was measured, and the results suggest that there are no differences in the photodynamic activity of Photofrin and Photogem when irradiated with the blue, green and red light, if the effect of the molar absorption coefficient and the effect of light penetration in the tissue are taking into account. We report the ID 10 (irradiation dose responsible for killing 90% of cells) for Photofrin and Photogem irradiated in the three wavelengths. The fact that melanoma cells have problems with the absorption of the light due to poor penetration of the light administrated in PDT (red light: 630 nm) suggests that the melanoma cells can be irradiated with blue and green light producing the same cytotoxic result, only with an adjustment of the light dose. This may offer a means to improve clinical PDT for patients with this diagnosis.
Background
Ionizing radiation (IR) initiates intracellular oxidative stress through enhanced formation of reactive oxygen species (ROS) that attack DNA leading to cell death. As the diversity of IR applied in medicine, agriculture, industry, and the growing threats of global terrorism, the acquisition of radioprotectors is an urgent need for the nation. However, the applicability of radioprotectors currently under investigation is limited due to their inherent toxicity.
Objective
This study investigated the effect of a standardized North American ginseng extract (NAGE, total ginsenoside content: 11.7%) on DNA damage in human lymphocytes at 90 min post-irradiation.
Design
With the application of NAGE (250 – 1000 µg ml−1) at 90 min post-irradiation (1 and 2 Gy), DNA damage in lymphocytes obtained from 40 healthy individuals was evaluated by cytokinesis-block micronucleus (CBMN) assay. Similar experiments were also performed in lymphocytes treated with WR-1065 (1 mM or 3mM). In addition, before and after irradiation, lymphocytes obtained from 10 individuals were measured for their total antioxidant capacity (TAC) and the reactive oxygen species (ROS).
Results
The significant effect of NAGE against 137Cs-induced MN in lymphocytes is concentration-dependent. NAGE (750 µg ml−1) reduced MN yield by 50.7% after 1 Gy and 35.9% after 2 Gy exposures, respectively; these results were comparable to that of WR-1065. Further, we also found that NAGE reduces MN yield and ROS but increases TAC in lymphocytes.
Conclusions
Our results suggest that NAGE is a relatively non-toxic natural compound that holds radioprotective potential in human lymphocytes even when applied at 90 min post-irradiation. One of the radioprotective mechanisms may be mediated through the scavenging of free radicals and enhancement of the intracellular TAC.
In order to diagnose colon cancer at an earlier, more localized stage, there is a need to develop diagnostic markers (genes) which can detect early patterns of gene expression in exfoliated colonocytes shed in the stool during routine screening for this disease. An RNA-based detection is more pertinent than either a DNA-based or a protein-based method as a screening procedure, but it has not been widely used as a cancer screen because of the difficulty of handling and stabilizing the RNA molecule. We describe a method that permits extraction of intact nondegraded total RNA from human colonocytes in stool and from normal and malignant colon tissues (which were employed for comparison with stool). Because it utilizes commercially available kits, this method is simpler than other published methods and does not require isolation of messenger (m)RNA, thereby reducing the chances of contaminating the preparations with degrading nucleases, and even a small amount of isolated total RNA can be adequately reverse transcribed, making high-quality copy (c) DNA. This is followed by PCR (either qualitative end point or semiquantitative real-time) using colon cancer-specific gene primers. By routinely and systematically being able to perform quantitative gene expression measurements on noninvasive samples, the goal of this pilot work is to lay the groundwork for conducting a large clinical study to identify groups of selected genes whose expression is consistently altered at an early stage in the neoplastic process. Such work will permit noninvasive monitoring of at-risk patients through the analysis of their stool samples. Correct diagnosis will allow for surgical and/or other interventions before the tumor is well established and, thus, should decrease mortality from this preventable disease.
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