DNA repair in cultured mouse cells of increasing population doubling level

Belle, Michael La; Linn, Stuart

doi:10.1016/0167-8817(84)90066-x

Cited by 17 publications

(7 citation statements)

References 40 publications

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“…These results were confirmed by La Belle and Linn [1984] who also reported diminished UDS at increased population doubling level with BALB/c mice. Yagi [1982] documented a reduction in UDS in cells from increasing passages from the primary cultures derived from embryos of three different mouse strains.…”

Section: The Rodent Repairadoxsupporting

confidence: 91%

Revisiting the rodent repairadox

Hanawalt

2001

Environ and Mol Mutagen

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Cultured rodent and human cells typically display similar clonal survival characteristics following exposure to ultraviolet light (UV). However, compared to human cells, cultured cells from mice, rats, and hamsters are generally deficient in excision repair of the most prominent DNA lesion produced by UV, the cyclobutane pyrimidine dimer. In light of recent studies on the control of nucleotide excision repair, we are beginning to understand the basis for this so-called "repairadox." The resolution of this issue is important because rodents are so widely employed as surrogates for humans in genetic toxicology. This article will review the evolution in our understanding of rodent DNA repair and will also "revisit" my early association with my graduate mentor and esteemed colleague, Dick Setlow, in his honor upon the attainment of his 80th birthday.

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Section: The Rodent Repairadoxsupporting

confidence: 91%

Revisiting the rodent repairadox

Hanawalt

2001

Environ and Mol Mutagen

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“…In this context. it should be noted that the levels of HAP1 in primary cells have been reported to be much lower than those in immortal cell lines (La-Belle andLin. 1984: Chen et al 1991).…”

Section: Resultsmentioning

confidence: 90%

Levels of the DNA repair enzyme human apurinic/apyrimidinic endonuclease (APE1, APEX, Ref-1) are associated with the intrinsic radiosensitivity of cervical cancers

Herring

West²,

Wilks³

et al. 1998

Br J Cancer

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Summary A study was made of the relatonship between the intrinsic radiosensifivity of human cervical tumours and the expression of the DNA repair enzyme human apurnic/apyrmidinic endonuclease (HAP1). The radiosensitivity of clonogenic cells in tumour biopsies was measured as surviving fraction at 2 Gy (SF2) using a soft agar assay. HAP1 expression levels were determined after staining of formalin-fixed paraffin-embedded tumour sections with a rabbit antiserum raised against recombinant HAP1. Both measurements were obtained on pretreatment biopsy material. All 25 tumours examined showed positive staining for HAP1, but there was heterogeneity in the level of expression both within and between tumours. The average coefficients of variation for intra-and intertumour heterogeneity were 620o and 82% respectively. There was a moderate but significant positive correlation between the levels of HAP1 expression and SF2 (r= 0.60, P = 0.002). Hence, this study shows that there is some relationship between intrinsic radiosensitivity and expression of a DNA repair enzyme in cervical carcinomas. The resutts suggest that this type of approach may be useful in the development of rapid predictive tests of tumour radiosensitivity.

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“…Whilst HAP1 may represent one among many factors that are important in toxicity, its effects may only become evident in specific circumstances and in a limited number of cell types. The levels of HAP1 have been reported to be 6-20 times higher in established cell lines than in primary cells LaBelle and Linn, 1984), and HAP1 levels may therefore be more critical in the latter. This would be consistent with the significant correlation found between the levels of HAP1 expression detected in fixed tumour biopsies and the radiosensitivity of cells primary-cultured from them (Herring et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Expression levels of the DNA repair enzyme HAP1 do not correlate with the radiosensitivities of human or HAP1-transfected rat cell lines

et al. 1999

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The base-excision repair pathway has evolved to repair a diverse range of base modifications and base losses as well as damage to the sugar-phosphate backbone of DNA. This damage may arise through spontaneous base hydrolysis (Lindahl and Anderson, 1972), endogenous oxidative metabolism (Lindahl, 1990), or exposure to genotoxic agents, including agents that exert their effects via the formation of reactive oxygen species, such as peroxides and ionizing radiation (reviewed by Demple and Harrison, 1994).The major cytotoxic lesion following exposure of cells to ionizing radiation is considered to be the DNA double-strand break (dsb) associated with other lesions in damage complexes termed local-multiply (or regional)-damaged sites (Ward et al, 1994). However, apurinic/apyrimidinic (AP) sites are major lesions resulting from the direct effects of radiation on DNA bases or following glycosylase-mediated excision of specific modified bases. The action of AP endonucleases on these AP sites produces single-strand breaks that are likely to contribute to the formation of dsb if they are in close proximity to other lesions. Disruption of the sugar-phosphate backbone of DNA also occurs causing strand breaks with atypical termini (Teoule, 1987). These include 3′ phosphate and 3′-phosphoglycolate termini which cannot be used as primers for DNA synthesis by Escherichia coli DNA polymerase I or T4 DNA polymerase (Henner et al, 1983), since a 3′ hydroxyl terminus is required. Consequently, these 3′ terminal modified deoxyribose moieties constitute blocks to DNA repair synthesis.If unrepaired, both AP sites and 3′ blocked termini can be toxic (Demple et al, 1986), and AP sites can also be mutagenic (Loeb and Preston, 1986). The major cellular enzymes responsible for initiating the repair of these sites are class II AP endonucleases (reviewed by Doetsch and Cunningham, 1990;Demple and Harrison, 1994;Barzilay and Hickson, 1995). AP endonucleases incise the phosphodiester backbone 5′ to the abasic site to generate 3′ phosphate and 5′ deoxyribose phosphate termini. Additionally, the 3′-diesterase activity processes blocked 3′ termini to produce 3′ hydroxyl termini (Demple and Harrison, 1994;Winters et al, 1994). The 5′ deoxyribose phosphate group is excised by a deoxyribose phosphodiesterase, giving 5′ phosphate, and the single nucleotide gap thus generated can be filled by a DNA polymerase and repair completed by a DNA ligase.In Summary Apurinic/apyrimidinic (AP) sites in DNA are potentially lethal and mutagenic. They can arise spontaneously or following DNA damage from reactive oxygen species or alkylating agents, and they constitute a significant product of DNA damage following cellular exposure to ionizing radiation. The major AP endonuclease responsible for initiating the repair of these and other DNA lesions in human cells is HAP1, which also possesses a redox function. We have determined the cellular levels of this enzyme in 11 human tumour and fibroblast cell lines in relation to clonogenic survival following ionizing radiati...

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DNA repair in cultured mouse cells of increasing population doubling level

Cited by 17 publications

References 40 publications

Revisiting the rodent repairadox

Revisiting the rodent repairadox

Levels of the DNA repair enzyme human apurinic/apyrimidinic endonuclease (APE1, APEX, Ref-1) are associated with the intrinsic radiosensitivity of cervical cancers

Expression levels of the DNA repair enzyme HAP1 do not correlate with the radiosensitivities of human or HAP1-transfected rat cell lines

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