Thiols can either enhance or suppress DNA damage induction by catecholestrogens

Thibodeau, Paul A; Kocsis-Bédard, Suzanne; Courteau, Josiane; Niyonsenga, Théophile; Paquette, Benoît

doi:10.1016/s0891-5849(00)00446-9

Cited by 30 publications

(18 citation statements)

References 35 publications

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“…NAC is able to reduce Copper (II) to Cu (I), stimulate Cu (I)-dependent H 2 O 2 production and subsequent oxidative damage to DNA, and thereby is suggested to have both carcinogenic and anticarcinogenic activities. NAC slightly enhanced DNA oxidative damage generated by an estrogen (4-hydroxyesterdiol) and Cu (II) [127,128]. A fivefold reduction of ROS by NAC in colon carcinoma cells increases the proapoptotic, bax gene expression and effectiveness of chemotherapeutic agent, 5 fluorouracil [129].…”

Section: N-acetylcysteine In Cancermentioning

confidence: 98%

Molecular mechanisms of N -acetylcysteine actions

Zafarullah¹,

Li²,

Sylvester³

et al. 2003

Cellular and Molecular Life Sciences (CMLS)

1,194

879

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Oxidative stress generated by an imbalance between reactive oxygen species (ROS) and antioxidants contributes to the pathogenesis of arthritis, cancer, cardiovascular, liver and respiratory diseases. Proinflammatory cytokines and growth factors stimulate ROS production as signaling mediators. Antioxidants such as N-acetylcysteine (NAC) have been used as tools for investigating the role of ROS in numerous biological and pathological processes. NAC inhibits activation of c-Jun N-terminal kinase, p38 MAP kinase and redox-sensitive activating protein-1 and nuclear factor kappa B transcription factor activities regulating expression of numerous genes. NAC can also prevent apoptosis and promote cell survival by activating extracellular signal-regulated kinase pathway, a concept useful for treating certain degenerative diseases. NAC directly modifies the activity of several proteins by its reducing activity. Despite its nonspecificity, ability to modify DNA and multiple molecular modes of action, NAC has therapeutic value for reducing endothelial dysfunction, inflammation, fibrosis, invasion, cartilage erosion, acetaminophen detoxification and transplant prolongation.

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Section: N-acetylcysteine In Cancermentioning

confidence: 98%

Molecular mechanisms of N -acetylcysteine actions

Zafarullah¹,

Li²,

Sylvester³

et al. 2003

Cellular and Molecular Life Sciences (CMLS)

1,194

879

View full text Add to dashboard Cite

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“…Evaluating these changes in plasmid conformation is a more sensitive method for assessing DNA damage than estimating the formation of 8-oxo-7,8-dihydro-2 0 -deoxyguanosine (8-OHdG) by chromatography [Yang et al, 1999]. The plasmid assay has been used previously to study the pro-oxidant and antioxidant properties of various compounds [Thibodeau et al, 2001;Pankaj et al,in press]. In the present study, exposure of plasmid DNA to 50 Gy of radiation resulted in significant amounts of both single-strand and double-strand DNA breaks as judged by the loss of intact supercoiled DNA and the formation of open circular and linear forms.…”

Section: Discussionmentioning

confidence: 99%

Protection from radiation‐induced mitochondrial and genomic DNA damage by an extract of Hippophae rhamnoides

Shukla

Chaudhary

Kumar

et al. 2006

Environ and Mol Mutagen

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Hippophae rhamnoides or seabuckthorn is used extensively in Indian and Tibetan traditional medicine for the treatment of circulatory disorders, ischemic heart disease, hepatic injury, and neoplasia. In the present study, we have evaluated the radioprotective potential of REC-1001, a fraction isolated from the berries of H. rhamnoides. Chemical analysis of the extract indicated that REC-1001 was approximately 68% by weight polyphenols, and contained kaempferol, isorhamnetin, and quercetin. The effect of REC-1001 on modulating radiation-induced DNA damage was determined in murine thymocytes by measuring nonspecific nuclear DNA damage at the whole genome level using the alkaline halo assay and by measuring sequence/gene-specific DNA damage both in nuclear DNA (beta-globin gene) and in mitochondrial DNA using a quantitative polymerase chain reaction. Treatment with 10 Gy resulted in a significant amount of DNA damage in the halo assay and reductions in the amplification of both the beta-globin gene and mitochondrial DNA. REC-1001 dose-dependently reduced the amount of damage detected in each assay, with the maximum protective effects observed at the highest REC-1001 dose evaluated (250 micro g/ml). Studies measuring the nicking of naked plasmid DNA further established the radioprotective effect of REC-1001. To elucidate possible mechanisms of action, the antioxidant properties and the free-radical scavenging activities of REC-1001 were evaluated. REC-1001 dose-dependently scavenged radiation-induced hydroxyl radicals, chemically-generated superoxide anions, stabilized DPPH radicals, and reduced Fe(3+) to Fe(2+). The results of the study indicate that the REC-1001 extract of H. rhamnoides protects mitochondrial and genomic DNA from radiation-induced damage. The polyphenols/flavonoids present in the extract might be responsible for the free radical scavenging and DNA protection afforded by REC-1001.

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“…ROS can also be formed after electron escape from the mitochondria of proliferating cells, favored by high rates of multiplication and metabolism and increased activity of mitochondrial superoxide dismutase (Mn-SOD) [39,40] or, in human placental mitochondria, after interaction between NADPH and iron [41]. Other sources of ROS are increased activities of NADPH oxidases by contact between tissues from the embryo and mother or between replicating cells [33], interactions between estrogens and minerals [42] or triggering of NADPH peroxidases associated to the membranes inside the cells [43].…”

Section: Origin Of Ros Production During Gestationmentioning

confidence: 99%

“…Direct formation of O −• 2 production at the level of the nuclear membrane through an NAD(P)H dependent mechanism is possibly of major importance and can end in the interaction of this radical with iron to produce • OH [43]. More means of • OH formation can be recruited, such as interactions between H 2 O 2 or O −• 2 and iron [17] or interactions between various peroxides of proteins, lipids or catechols and redox minerals [2,10,42,46]. In those instances, high rates of storage of iron occur in the placenta and in the fetus observed in various species including the bovine, starting from the early stages of pregnancy [47] and can be released through many different mechanisms [48].…”

Section: Origin Of Ros Production During Gestationmentioning

confidence: 99%

“…In those instances, high rates of storage of iron occur in the placenta and in the fetus observed in various species including the bovine, starting from the early stages of pregnancy [47] and can be released through many different mechanisms [48]. The • OH radical seems essential in several pathways of signal transduction, although it also induces risks of severe oxidative stress [42,43,49].…”

Section: Origin Of Ros Production During Gestationmentioning

confidence: 99%

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Gestation linked radical oxygen species fluxes and vitamins and trace mineral deficiencies in the ruminant

2006

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-In mammals, radical oxygen species (ROS) are essential factors of cell replication, differentiation and growth (oxidative signal), notably during gestation, but are also potentially damaging agents. In Women, ROS play a role in remodeling of uterine tissues, implantation of the embryo, settlement of the villi and development of blood vessels characteristic of gestation. The body stores of vitamins and minerals of gestating females are used to keep ROS fluxes at a level corresponding to oxidative signals and to prevent an imbalance between their production and scavenging (oxidative stress), which would be detrimental to the mother and fetus. There is some evidence that, although based on different regulatory mechanisms, most of the effects of ROS reported in humans also occur in pregnant ruminant females, some of which have been actually reported. Many vitamins and trace elements have dual effects in the organism of mammals: (a) they are involved in the control of metabolic pathways or/and gene expression, (b) but most of the time they also display ROS trapping activity or their deficiencies induce high rates of ROS production. Deficiencies induce different disorders of gestation and can be induced by different kinds of stress. An example is given, corresponding to the decreased contents of cobalt of forages, when exposed to sustained heavy rains, so that the supply of vitamins B12 to the organism of the ruminant that grazes them is reduced and failure of gestation is induced. Outdoor exposure of ruminants to adverse climatic conditions by itself can increase the vitamin and trace element requirements. Adaptation of production systems taking into account these interactions between gestation and sources of stress or change of the quality of feeding stuffs as well as further developments of knowledge in that field is necessary to promote sustainable agricultural practices.gestation / ovine / bovine / vitamins / trace elements / antioxidant enzymes / radical oxygen species / radical phenomena

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Thiols can either enhance or suppress DNA damage induction by catecholestrogens

Cited by 30 publications

References 35 publications

Molecular mechanisms of N -acetylcysteine actions

Molecular mechanisms of N -acetylcysteine actions

Protection from radiation‐induced mitochondrial and genomic DNA damage by an extract of Hippophae rhamnoides

Gestation linked radical oxygen species fluxes and vitamins and trace mineral deficiencies in the ruminant

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