Individual capacity for detoxification of genotoxic compounds and repair of DNA damage. Commonly used methods for assessment of capacity for DNA repair

Chakarov, Stoyan; Petkova, Rumena; Russev, George

doi:10.7750/biodiscovery.2014.11.2

Cited by 10 publications

(14 citation statements)

References 332 publications

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“…On organism level, high capacity to maintain genomic integrity may also be a good thing. It is believed that individuals with higher-than-average capacity for detection and repair of genomic damage may be at decreased risk for many of the common adult-onset diseases and may have increased reproductive fitness [8,9]. On a population and species level, however, groups of individuals that maintain very strictly the integrity of their genome may eventually doom themselves to genetic stagnation.…”

Section: Degenerative Disease or Cancer? Make Your Choicementioning

confidence: 99%

[No] Need for Speed: Late-onset Diseases as Evolution's Power Brakes

Petkova¹,

Chakarov²

2018

Cell Dev Biol

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Degenerative disease and cancer are the top causes of death in middle and advanced age and it seems that this trend will continue, at least in the near future. Modern medicine has an impressive arsenal of methods and tools to detect monitor and control a wide variety of diseases and conditions, including diseases with onset in middle and advanced age. Nevertheless, they are very rarely completely cured. Why, despite all the efforts of research and healthcare, we still keep failing in our efforts to cure late-onset diseases? It might be that we are trying to fight against laws of Nature that were purposely put in place so that evolution may go on but could not advance before its time.Relatively recently, we proposed the hypothesis that 'death of old age' and cancer may be viewed as Nature-made mechanisms or larger-scale checkpoints that keep the rate of evolution in check and preserve the population and the species at the expense of individuals. At this point in our development, we cannot change the rules of Nature. It is within our power, however, to anticipate, prevent and modify the outcomes of late-onset disease. Thus, we ought to keep on with research and development aimed at management of late-onset disease and improving the quality of life for the patients.

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Section: Degenerative Disease or Cancer? Make Your Choicementioning

confidence: 99%

[No] Need for Speed: Late-onset Diseases as Evolution's Power Brakes

Petkova¹,

Chakarov²

2018

Cell Dev Biol

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“…In the case of normal repair capacity plus 'pro-repair' genotype there may be risk that cancer may occur at later age. At the same time, there may be increased likelihood that genotoxic anticancer treatments may be successful, as cancer cells with decreased repair capacity are more prone to die or arrest their rapid division under conditions of increased genotoxic stress inflicted by genotoxic therapy [32,168]. Thus, individuals with normal repair capacity plus 'prorepair' genotype may live well into old age as cancer survivors.…”

Section: Don't Throw Away Repair It -Capacity To Repair Genotoxic Damentioning

confidence: 99%

APOE4, oxidative stress and decreased repair capacity - a no-brainer. Faulty lipid metabolism and increased levels of oxidative damage may be risk factors in the pathogenesis of late-onset dementia

Nayyar

Chakalova²

2015

Biodiscovery

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Keywords: Late-onset disease, dementia, APOE, mitochondrial DNA, individual repair capacity.Abbreviations: AD -Alzheimer's disease, APOE -apolipoprotein E, ATP -adenosine triphosphate, BER -base excision repair, CAA -cerebral amyloid angiopathy, CNS -central nervous system, FTD -frontotemporal dementia, HD -Huntington's disease, IMT -intimamedia thickness, IRC -individual repair capacity, MCI -mild cognitive impairment, MND -motor neuron disease, NER -nucleotide excision repair, NMDA -N-methyl-D-aspartate, PD -Parkinson's disease, PDAPP -PDGF promoter expressing amyloid precursor protein, ROS -reactive oxygen species; SOD -superoxide dismutase, VCI -vascular cognitive decline.* Corresponding Authors: Ashima Nayyar, email: a.nayyar@abertay.ac.uk Conflict of Interests:No potential conflict of interest was disclosed by any of the authors. AbstractDementia is very common in the elderly and its incidence increases in an age-dependent fashion. Alzheimer's disease and vascular cognitive decline are the most common cases of dementia in the elderly. Amyloid burden and increased levels of oxidative damage have been implicated to play significant roles in the pathogenesis of late-onset dementia. In this paper we propose that there are three major genetic factors that may modulate the risk for dementia in later life: carriership of APOE variant alleles, carriership of mitochondrial DNA of haplogroups associated with ineffective oxygen utilisation (specifically, haplogroup H) and carriership of genetic polymorphisms conferring subtly deficient DNA repair. All three factors are quite common in the European populations. Each of these three factors may not have significant effect on the phenotype when taken separately, but when combined in the same genotype, the effects may be cumulative. Further studies are needed in order to elucidate the genotype-phenotype relationships and provide a reliable basis for assessment of the genetic risk for sporadic late-onset dementia. Lifestyle alterations and therapies targeted at decreasing the oxidative burden to aging cells and tissues may decrease the risk for neurological decline in later life.

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“…Even among the clinically healthy individuals, however, the response to DNA damage may greatly vary. It is currently believed that individual radioresistance is determined by a variety of factors, including specificities in the genetic background, specificities in the physiology of the cells and tissues that received the irradiation, and environmental factors [7,8].…”

Section: Individual Capacity For Dna Repairmentioning

confidence: 99%

Some problems and errors in cytogenetic biodosimetry

Mosse

Kilchevsky

Nikolova

et al. 2016

Biotechnology & Biotechnological Equipment

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Human radiosensitivity is a quantitative trait that is generally subject to binomial distribution. Individual radiosensitivity, however, may deviate significantly from the mean (by 2-3 standard deviations). Thus, the same dose of radiation may result in different levels of genotoxic damage (commonly measured as chromosome aberration rates) in different individuals. There is significant genetic component in individual radiosensitivity. It is related to carriership of variant alleles of various single-nucleotide polymorphisms (most of these in genes coding for proteins functioning in DNA damage identification and repair); carriership of a different number of alleles producing cumulative effects; amplification of gene copies coding for proteins responsible for radioresistance, mobile genetic elements and others. Among the other factors influencing individual radioresistance are: the radioadaptive response; the bystander effect; the levels of endogenous substances with radioprotective and antimutagenic properties and environmental factors such as lifestyle and diet, physical activity, psychoemotional state, hormonal state, certain drugs, infections and others. These factors may have radioprotective or sensibilizing effects. Apparently, there are too many factors that may significantly modulate the biological effects of ionizing radiation. Thus, conventional methodologies for biodosimetry (specifically, cytogenetic methods) may produce significant errors if personal traits that may affect radioresistance are not accounted for.

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Individual capacity for detoxification of genotoxic compounds and repair of DNA damage. Commonly used methods for assessment of capacity for DNA repair

Cited by 10 publications

References 332 publications

[No] Need for Speed: Late-onset Diseases as Evolution's Power Brakes

[No] Need for Speed: Late-onset Diseases as Evolution's Power Brakes

APOE4, oxidative stress and decreased repair capacity - a no-brainer. Faulty lipid metabolism and increased levels of oxidative damage may be risk factors in the pathogenesis of late-onset dementia

Some problems and errors in cytogenetic biodosimetry

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