The DNA damage response - from cell biology to human disease

Lam, Fred C.

doi:10.20517/jtgg.2021.61

Cited by 17 publications

(10 citation statements)

References 106 publications

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“…Living organisms are continually exposed to sources of DNA damage, both endogenous and exogenous, which can significantly impact health and contribute to various diseases [59]. Studies consistently show that patients with mamary cancer exhibit notably higher levels of initial endogenous DNA damage compared to healthy individuals [59,60,61]. In response to these genetic challenges, cells have evolved complex mechanisms to safeguard genome stability, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination (HR), and nonhomologous end-joining (NHEJ) [62,63].…”

Section: Resultsmentioning

confidence: 99%

Assessment of metronomic chemotherapy–induced DNA damage in peripheral blood leukocytes from canine mammary cancer patients using the alkaline comet assay

Chalco–Torres,

Aranguren–Méndez,

Guerrero–López

et al. 2024

RC FCV-LUZ

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Mammary cancer is a disease that requires effective treatments. Conventional chemotherapy, while effective, often causes harmful side effects. In contrast, metronomic chemotherapy (mCHT), which involves the continuous administration of low doses of anticancer drugs, is presented as a less aggressive alternative. In this study, the genotoxic impact of treatment with Cyclophosphamide and Meloxicam under the mCHT approach was evaluated in ten canine (Canis lupus familiaris) patients with mammary carcinoma after undergoing mastectomy. The patients underwent monthly evaluations, including chest X–rays, blood tests, and the alkaline comet assay to measure genotoxic effects of the antineoplastic drugs. These results were compared with those of a group that received conventional chemotherapy. The results revealed that patients treated with mCHT experienced significantly lower levels of DNA damage compared to those who received conventional chemotherapy. Furthermore, DNA damage decreased over time during mCHT, suggesting that dogs may have developed tolerance to the treatment. Blood parameters remained stable in the mCHT–treated group, and X–rays showed no signs of recurrence or metastasis. All dogs survived during the one–year follow–up without mammary cancer recurrence. It is concluded that mCHT with Cyclophosphamide appears to be a less aggressive therapeutic option with a more favorable genotoxic profile in the treatment of mammary cancer in dogs.

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Section: Resultsmentioning

confidence: 99%

Assessment of metronomic chemotherapy–induced DNA damage in peripheral blood leukocytes from canine mammary cancer patients using the alkaline comet assay

Chalco–Torres,

Aranguren–Méndez,

Guerrero–López

et al. 2024

RC FCV-LUZ

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“…In particular, intrinsic apoptosis pathway is triggered by DNA and oxidative damage, which are linked with disruption of the mitochondrial membrane potential (MMP), increase of cytochrome c (Cyt c) release, and apoptosis induction ( McDonald et al., 2022 ). Precisely, from the comparison between rhein and Cassia angustifolia , several proteins involved in DNA damage repair were uniquely identified in rhein-treated samples, suggesting a potential genotoxic chemical exposure ( Lam, 2022 ). These are the following:…”

Section: Resultsmentioning

confidence: 99%

Hydroxyanthracene derivates citotoxicity: A differential evaluation between single molecule and whole plant extract

et al. 2023

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Hydroxyanthracene derivates (HADs) are a group of natural or synthetic compounds with a wide range of biological activities (for instance, anti-inflammatory, antibacterial, and antiarthritic). In addition, because of their properties for helping the normal bowel function, HADs are widely used in constipation as pharmacological drugs and nutritional supplements. Nevertheless, during the past years, a safety usage of HAD products has been under consideration because some studies reported that HADs are not lacking toxicity (i.e., genotoxic and carcinogenic activity). Thus, the first objective of this study is to shed light on the large variability in composition of botanical food supplements containing HAD by a systematic analysis of the qualitative and quantitative composition of a cohort of extracts and raw materials of plants with high levels of anthraquinones commercially available (Cassia angustifolia, Rhamnus purshiana, Rhamnus frangula, Rheum palmatum, and Rheum raponticum). To date, the investigation of HAD toxicity was based on in vitro and in vivo studies conducted mainly on the use of the single molecules (emodin, aloe-emodin, and rhein) rather than on the whole plant extract. The qualitative-quantitative characterization was the starting point to select the most appropriate products to be used as treatment for our in vitro cell studies. Thus, the second objective of this study is the investigation, for the first time, of the toxic events of HAD used as single molecule in comparison with the whole plant extracts containing HAD in an intestinal in vitro model using human colorectal adenocarcinoma cells (Caco-2). In addition, a shotgun proteomics approach was applied to profile the differential protein expression in the Caco-2 cells after a single-HAD or whole–plant extract treatment to fully understand the potential targets and signaling pathways. In conclusion, the combination of a detailed phytochemical characterization of HAD products and a largely accurate analysis of the proteomic profile of intestinal cells treated with HAD products provided the opportunity to investigate their effects in the intestinal system.

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“…It is now commonly accepted that when the magnitude of DNA lesions overwhelms the skin's DNA repair capacity, an un-repaired or un-removed mutant may have an opportunity to eventually develop into a skin cancer [21][22][23]. Interestingly, strong sunlight can produce up to 100,000 DNA lesions per skin cell per hour [24][25][26]. It was suggested that the SS, caused by strong sunlight primarily attributed to UVB rays, can overwhelm a skin cell's DNA repair capacity and can potentially trigger the development of skin cancer [10].…”

Section: Ss Overwhelms the Dna Repair Mechanismsmentioning

confidence: 99%

Prevention of Skin Cancer: Healthy Sun Exposure and No sunscreen for Intense Intermittent Exposure; Photoaging Theories Questioned and New Strategies

Chiou¹

2022

JDR

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Currently the FDA adopts a zero-tolerance policy toward sun exposure in order to prevent skin cancer and premature skin aging (photoaging). This is apparently based on classical concept that damage from sunlight, a carcinogen, is cumulative and un-reparable. Such concept is apparently flawed both theoretically and in reality. The nature’s design to achieve genomic stability of body health and appearance for smooth passage of generations in our normal daily lives would require virtually complete repair of damages of DNA and other tissue components from daily Exposure to Non-Burning Sunlight (ENS). In other words, ENS is generally not expected to cause skin cancer and photoaging. Such notion is evidenced by, for example, low worldwide skin-cancer incidences, severe sunburn as overwhelming skin-cancer etiology, and intrinsic aging as overwhelming skin aging. Since ENS can provide numerous health benefits, such exposure can be regarded as healthy sun exposure and used to help prevent skin cancer. Due to unintended sunburn effect, use of sunscreens for intense intermittent exposure is strongly discouraged. As photoaging and skin cancer may be closely related, some questions related to conventional theories and practices in photoaging are also raised. They include the following: Schuster’s pioneering study in 1975; invalidation of accelerated aging theory; questionable theory on etiology of wrinkles and age spots; Fisher’s studies on metalloproteinases; bolus doing vs constant-rate dosing in irradiation; moisturizers as anti-photoaging/anti-cancer agents; inclusion of blood and water in skin-aging exosome; wind effect; differences in usage pattern between countries in sunscreen evaluation; replacement of UVA in tanning beds.

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The DNA damage response - from cell biology to human disease

Cited by 17 publications

References 106 publications

Assessment of metronomic chemotherapy–induced DNA damage in peripheral blood leukocytes from canine mammary cancer patients using the alkaline comet assay

Assessment of metronomic chemotherapy–induced DNA damage in peripheral blood leukocytes from canine mammary cancer patients using the alkaline comet assay

Hydroxyanthracene derivates citotoxicity: A differential evaluation between single molecule and whole plant extract

Prevention of Skin Cancer: Healthy Sun Exposure and No sunscreen for Intense Intermittent Exposure; Photoaging Theories Questioned and New Strategies

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