In vivo human somatic mutation: frequency and spectrum with age

Scott, G. B. D.; McCarron, M.A.; Kutlaca, A.; Turner, David R.; Morley, Alexander A.

doi:10.1016/0027-5107(92)90186-6

Cited by 141 publications

(63 citation statements)

References 11 publications

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“…The geometric mean frequency increased from 0.71x10 -5 in neonates to 6.53x10 -5 in the elderly (Grist et al, 1992). Similarly, stable chromosome aberrations that increased in frequency with increasing age were observed in human peripheral lymphocytes (Vorobtsova et al, 2001).…”

Section: The Experimental Datamentioning

confidence: 79%

Does age influence loss of heterozygosity?

Carr

Gottschling

2008

Experimental Gerontology

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The striking correlation between advanced age and an increased incidence of cancer has led investigators to examine the influence of aging on genome maintenance.Because loss of heterozygosity (LOH) can lead to the inactivation of tumor suppressor genes, and thus carcinogenesis, understanding the affect of aging on this type of mutation event is particularly important. Several factors may affect the rate of LOH, including an increase in the amount of DNA damage, specifically double-strand breaks (DSB), and the ability to efficiently repair this damage via pathways that minimize the loss of genetic information. Because of experimental constraints, there is only suggestive evidence for a change in the rate of DNA damage as humans age. However, recent studies in model organisms find that there are increased rates of LOH with age, and that repair of DNA damage occurs via a different pathway in old cells versus young cells. We speculate that the age-dependent change in DNA repair may explain why there is increased LOH, and that the findings from these model organisms may extend to humans.

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Section: The Experimental Datamentioning

confidence: 79%

Does age influence loss of heterozygosity?

Carr

Gottschling

2008

Experimental Gerontology

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“…This may be explained on the basis of mutational event at the regulatory system of an unexpected gene (s) that activate it (Abdelsalam et al, 1997). The changes in band intensity could be explained on the basis of induction of gene mutation at the regulatory system which modulates, attenuates or increases transcription rate of a particular structural gene (Grist et al, 1992). According to El-Abidin Salam et al (1993) the recorded changes in band intensity could be attributed to the cytological abnormalities.…”

Section: Biochemcial Analysismentioning

confidence: 99%

Mutagenic Potential of Imazethapyr Herbicide (Pursuit*) on Vicia faba in the Presence of Urea Fertilizer

El-Nahas¹

2000

Pakistan J. of Biological Sciences

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Imazethapyr herbicide (pursuit*) singly or combined with urea fertilizer on mitotic activity, inducation of mitotic and meiotic abnormalities and changes in the M2 seed storage protein banding patterns has been investigated on Vicia faba plants. A significant reduction in mitotic index was induced after different treatment in both forms (singly or combined). A variety of chromosomal abnormalities were observed in both mitotic and meiotic divisions respresented by stickiness, disturbance, laggards, bridges, multipolar, C-metaphase, breaks and micro and multinuclei. The frequency of these types of abnormalities decrease in case of pursuit herbicide combined with urea fertilizer. Electrophoretic analysis showed that pursuit and its combination with urea has a great ability to induce changes in the protein banding patterns of Vida faba seed storage protein as compared with untreated samples being more pronounced in treatment with the herbicide singly.

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“…In previous studies, LOH events were analyzed to measure the accumulation of cells harboring recombined DNA during aging [41,42]. Since LOH can be caused by multiple mechanisms, careful analysis of DNA must be done in order to reveal the fraction of events resulting from HR.…”

Section: Introductionmentioning

confidence: 99%

Tissue-specific differences in the accumulation of sequence rearrangements with age

et al. 2008

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Mitotic homologous recombination (HR) is a critical pathway for the accurate repair of DNA double strand breaks (DSBs) and broken replication forks. While generally error-free, HR can occur between misaligned sequences, resulting in deleterious sequence rearrangements that can contribute to cancer and aging. To learn more about the extent to which HR occurs in different tissues during the aging process, we used Fluorescent Yellow Direct Repeat (FYDR) mice in which an HR event in a transgene yields a fluorescent phenotype. Here, we show tissue-specific differences in the accumulation of recombinant cells with age. Unlike pancreas, which shows a dramatic 23-fold increase in recombinant cell frequency with age, skin shows no increase in vivo. In vitro studies indicate that juvenile and aged primary fibroblasts are similarly able to undergo HR in response to endogenous and exogenous DNA damage. Therefore, the lack of recombinant cell accumulation in the skin is most likely not due to an inability to undergo de novo HR events. We propose that tissue-specific differences in the accumulation of recombinant cells with age result from differences in the ability of recombinant cells to persist and clonally expand within tissues.

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In vivo human somatic mutation: frequency and spectrum with age

Cited by 141 publications

References 11 publications

Does age influence loss of heterozygosity?

Does age influence loss of heterozygosity?

Mutagenic Potential of Imazethapyr Herbicide (Pursuit*) on Vicia faba in the Presence of Urea Fertilizer

Tissue-specific differences in the accumulation of sequence rearrangements with age

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