The triage theory posits that modest micronutrient deficiencies may induce reallocation of nutrients to processes necessary for immediate survival at the expense of long-term health. Neglected processes could in time contribute to the onset of age-related diseases, in which oxidative stress is believed to be a major factor. Vitamin B12 (B12) appears to possess antioxidant properties. This review aims to summarise the potential antioxidant mechanisms of B12 and investigate B12 status in relation to oxidative stress markers. A systematic query-based search of PubMed was performed to identify eligible publications. The potential antioxidant properties of B12 include: (1) direct scavenging of reactive oxygen species (ROS), particularly superoxide; (2) indirect stimulation of ROS scavenging by preservation of glutathione; (3) modulation of cytokine and growth factor production to offer protection from immune response-induced oxidative stress; (4) reduction of homocysteine-induced oxidative stress; and (5) reduction of oxidative stress caused by advanced glycation end products. Some evidence appears to suggest that lower B12 status is related to increased pro-oxidant and decreased antioxidant status, both overall and for subclinically deficient individuals compared to those with normal B12 status. However, there is a lack of randomised controlled trials and prospective studies focusing specifically on the relation between B12 and oxidative stress in humans, resulting in a low strength of evidence. Further work is warranted.

https://www.mdpi.com/2072-6643/11/2/482/pdf

Vitamin B12 in Relation to Oxidative Stress: A Systematic Review.

Gross chromosomal rearrangements (including translocations, deletions, insertions and duplications) are a hallmark of cancer genomes and often create oncogenic fusion genes. An obligate step in the generation of such gross rearrangements is the formation of DNA double-strand breaks (DSBs). Since the genomic distribution of rearrangement breakpoints is non-random, intrinsic cellular factors may predispose certain genomic regions to breakage. Notably, certain DNA sequences with the potential to fold into secondary structures [potential non-B DNA structures (PONDS); e.g. triplexes, quadruplexes, hairpin/cruciforms, Z-DNA and single-stranded looped-out structures with implications in DNA replication and transcription] can stimulate the formation of DNA DSBs. Here, we tested the postulate that these DNA sequences might be found at, or in close proximity to, rearrangement breakpoints. By analyzing the distribution of PONDS-forming sequences within ±500 bases of 19 947 translocation and 46 365 sequence-characterized deletion breakpoints in cancer genomes, we find significant association between PONDS-forming repeats and cancer breakpoints. Specifically, (AT)n, (GAA)n and (GAAA)n constitute the most frequent repeats at translocation breakpoints, whereas A-tracts occur preferentially at deletion breakpoints. Translocation breakpoints near PONDS-forming repeats also recur in different individuals and patient tumor samples. Hence, PONDS-forming sequences represent an intrinsic risk factor for genomic rearrangements in cancer genomes.

/pdf/translocation-and-deletion-breakpoints-in-cancer-genomes-are-tniahxa4hw.pdf

Translocation and deletion breakpoints in cancer genomes are associated with potential non-B DNA-forming sequences.

Oxidized extracellular DNA as a stress signal that may modify response to anticancer therapy

Damage-associated molecular patterns in tumor radiotherapy.

Quantification of cell-free DNA in blood plasma and DNA damage degree in lymphocytes to evaluate dysregulation of apoptosis in schizophrenia patients.

Background 
Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases and acts upon the cells. Response to cfDNA depends on concentrations and levels of the damage within cfDNA. Oxidized extracellular DNA acts as a stress signal and elicits an adaptive response.


Principal Findings 
Here we show that oxidized extracellular DNA stimulates the survival of MCF-7 tumor cells. Importantly, in cells exposed to oxidized DNA, the suppression of cell death is accompanied by an increase in the markers of genome instability. Short-term exposure to oxidized DNA results in both single- and double strand DNA breaks. Longer treatments evoke a compensatory response that leads to a decrease in the levels of chromatin fragmentations across cell populations. Exposure to oxidized DNA leads to a decrease in the activity of NRF2 and an increase in the activity of NF-kB and STAT3. A model that describes the role of oxidized DNA released from apoptotic cells in tumor biology is proposed.


Conclusions/Significance 
Survival of cells with an unstable genome may substantially augment progression of malignancy. Further studies of the effects of extracellular DNA on malignant and normal cells are warranted.

/pdf/an-exposure-to-the-oxidized-dna-enhances-both-instability-of-4dvkjeew77.pdf

Tatiana V. Zolotukhina

Papers

An exposure to the oxidized DNA enhances both instability of genome and survival in cancer cells.