Direct comparison, in human resting lymphocytes, of the inter-individual variations in unscheduled DNA synthesis induced by N-acetoxy-2-acetylaminofluorene and ultraviolet irradiation

Pero, Ronald W.; Östlund, Catharina

doi:10.1016/0027-5107(80)90200-6

Cited by 33 publications

(10 citation statements)

References 26 publications

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“…If DNA repair capacity influences longevity, one would expect to see (1) an age-dependent decline in efficacy of repair and (2) that this decline is related to age-dependent functional decrements. Investigation of the role of DNA repair in vivo is complicated by inter-individual variability unrelated to age (Madden, Falek, Shafer andGlick 1979, Pero andOstlund 1980) and by differences in types of damage and types of repair, as well as in organ or tissue response (reviewed in Tice and Setlow 1985).…”

Section: Introduelionmentioning

confidence: 99%

Gender differences in age-related decline in DNA double-strand break damage and repair in lymphocytes

Mayer

Lange

Bradley

et al. 1991

Annals of Human Biology

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DNA repair capacity has been suggested to be a genetic mechanism which influences the rate of ageing and length of life. We recently reported an age-related decline in DNA double-strand break (DSB) repair in unstimulated human lymphocytes (Mayer, Lange, Bradley, and Nichols 1989, 1990). In that work peripheral lymphocytes isolated from whole blood donated by 20 normal, healthy subjects aged 23-78 years, were X-irradiated (30 Gy) on ice and incubated at 37 degrees C for repair times of 15, 30, and 120 min, and neutral filter elution was used to assay DSB induction and completeness of DSB rejoining. Further analysis reveals that the decrease in DSB rejoining appears to be more pronounced in older women than in older men (and may begin after age 65 years). Moreover the reported age-related decline in DSB induction occurs more rapidly (by a factor of ca. 2) in women than in men. We had previously demonstrated that, independently of in vivo age, cells with lower radiosensitivity (i.e. lesser DSB induction) appear to be less repair-proficient (Mayer et al. 1990). The present analysis reveals a gender-specific pattern in this correlation between extent of DSBs induced and percentage of DSBs rejoined: at comparable levels of DSB induction, cells from men rejoin a higher percentage of DSBs than do cells from women. This preliminary study suggests the following hypothesis: age-related DSB effects (i.e. induction and rejoining) are due to changes in chromatin structure and males are less sensitive than females to the influence which age-related alterations in chromatin exert on DSB effects.

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Section: Introduelionmentioning

confidence: 99%

Gender differences in age-related decline in DNA double-strand break damage and repair in lymphocytes

Mayer

Lange

Bradley

et al. 1991

Annals of Human Biology

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“…1 % gentamycin sulfate, 5 pgCi/ml 5H-thymidine, and 4 m,V/ hydroxyurea. Over 97% of the unstimulated mononuclear cells were in the Go phase of the cell cycle [9]. Hydroxyurea inhibits any residual replicative synthesis.…”

Section: In Vitro Dna Repair Assaymentioning

confidence: 99%

Correlates of Plasma Cortisol and DNA Repair in Human Peripheral Lymphocytes: Suppression of Repair in Women Taking Estrogen

O’Brien¹,

Larcom

Baxley

1993

Horm Res

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We have examined the relationship between total plasma cortisol concentration and DNA repair capacity in human peripheral lymphocytes cultured in vitro; the data indicate that high concentrations of cortisol ( > 20 µg/dl) inhibit DNA repair. The inhibitory effect can be abrogated by the addition of RU38486, a cortisol antagonist. In addition, we compared plasma cortisol concentration and in vitro DNA repair capacity in 52 healthy individuals. Females on therapeutic estrogen (oral contraceptive or estrogen replacement therapy) had significantly elevated plasma cortisol and suppression of DNA repair capacity.

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“…Specifically, significant interindividual varia on was observed in the responses of cultured human lymphocytes taken from healthy volunteers to DNA damage induced by chemical agents [1,2]. In their study group the authors found that samples taken from males exhibited higher levels of accumulated unrepaired DNA damage than samples from females and that the amount of accumulated persis ng damage increased with increasing age, arterial blood pressure and mortality rate in the respec ve age group.…”

Section: Emergence Of the Concept Of Normal Variance In Individual Camentioning

confidence: 78%

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

Chakarov¹,

Petkova²,

Russev³

2014

Biodiscovery

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The first part of this paper reviews the major achievements in the rapidly expanding field of research of individual capacity for repair of genotoxic damage. The issues of individual repair capacity are addressed from mul ple sides, analyzing the impact of the heritable components of the capacity for detoxifica on of genotoxic compounds, on the one hand (determining the risk for occurrence of DNA damage) and of the capacity for repair of DNA damage (when it has already occurred), on the other hand. The role of the capacity for repair of damage to DNA is discussed in the cons tu on of the risk for development of disease (mainly cancer, but also other common diseases and condi ons, such as diabetes, atherosclerosis and cardiovascular disease) and as a major factor in the outcomes of genotoxic therapies (eligibility for therapy with specific agents, risk for severe adverse effects, post-therapeu c survival rates, etc.). The paper contains an extensive list of biomarkers (mainly DNA polymorphisms, but also enzymes and other phenotypic markers, such as markers of the capacity for self-renewal of cell popula ons) that may be poten ally applicable in the assessment of the risk for carcinogenesis or for development other types of human disease.The second part of the paper provides a brief glimpse of the basic methodology used to obtain experimental results in assessment of the efficiency of DNA repair in living cells for research and diagnos c purposes.Cita on: Chakarov S, Petkova R, Russev GCh. Individual capacity for detoxifica on of genotoxic compounds and repair of DNA damage. Commonly used methods for assessment of capacity for DNA repair.

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Direct comparison, in human resting lymphocytes, of the inter-individual variations in unscheduled DNA synthesis induced by N-acetoxy-2-acetylaminofluorene and ultraviolet irradiation

Cited by 33 publications

References 26 publications

Gender differences in age-related decline in DNA double-strand break damage and repair in lymphocytes

Gender differences in age-related decline in DNA double-strand break damage and repair in lymphocytes

Correlates of Plasma Cortisol and DNA Repair in Human Peripheral Lymphocytes: Suppression of Repair in Women Taking Estrogen

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

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