Unscheduled DNA synthesis in confluent and mitotically arrested populations of aging human diploid fibroblasts

Dell’Orco, Robert T.; Whittle, W.L.

doi:10.1016/0047-6374(78)90027-1

Cited by 29 publications

(9 citation statements)

References 25 publications

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“…That the levels of UV-stimulated repair DNA synthesis in the fibroblasts as measured by autoradiography or an open-cell assay are not appreciably affected through mid-and late passages could be taken to agree with the conclusions of some reports (Smith and Hana-Walt, 1976;Dell'Orco and Whittle, 1978;Dell'Orco and Anderson, 1981;Cooke and Harris, 19811, but not others (Goldstein, 1971;Painter et al, 1973;Bowman et al, 1976;Hart and Setlow, 1976). Unfortunately, various assays that measure repair synthesis are complicated by the use of metabolic inhibitors, differential contributions of endogenous nucleotide pools, number of repair events, patch size, rate of DNA synthesis, and/or differences in the repair properties of cellular subpopulations, so that quantitative analyses utilizing one technique have given conclusions that differ from analyses with another technique.…”

Section: Discussionsupporting

confidence: 79%

Studies of DNA polymerases alpha and beta from cultured human cells in various replicative states

Krauss¹,

Linn²

1986

Journal Cellular Physiology

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DNA polymerase activities from HeLa cells and from cultured diploid human fibroblasts in various growth states were compared. alpha-Polymerase activities from log phase fibroblasts treated with sodium butyrate and from stationary phase HeLa cells had DEAE-cellulose elution patterns that differed from those of polymerases from dividing cells. Moreover, alpha- and beta-polymerases from nondividing cells replicated synthetic polymers less faithfully. Although similar changes were observed previously for polymerases from late-passage and postconfluent early passage fibroblasts, amounts of alpha-polymerase activity recovered from nondividing cells in this study did not dramatically decline as they had in the former cases. The alpha-polymerase activities from HeLa cells and fibroblasts in various growth states sedimented near 7.5S in 0.4 M KCI and could be inhibited by a monoclonal IgG fraction prepared against KB cell alpha-polymerase. By several criteria, there was no significant differences in levels of UV-stimulated repair synthesis observed in early or late-passage postconfluent fibroblasts or in log phase fibroblasts treated with sodium butyrate. In summary, levels of alpha-polymerase do not necessarily correlate either with replicative activity or with apparent levels of repair synthesis. However, cells with decreased replicative activity always yielded enzyme with decreased fidelity in vitro and altered chromatographic behavior. It appears, therefore, that the alterations observed for alpha-polymerase from late-passage cells may be attributed more generally to the nondividing nature of these cells.

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Section: Discussionsupporting

confidence: 79%

Studies of DNA polymerases alpha and beta from cultured human cells in various replicative states

Krauss¹,

Linn²

1986

Journal Cellular Physiology

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“…This suggestion also holds true for beta activity bound to the nuclear matrix (Table 4), the site of DNA synthesis, and hence, may be a reflection of a possible pre-or postreplicative screening role for this enzyme (see discussion by Smith and Berezney, 1982). Furthermore, the increase in polymerase beta activity also could be related to the increases in unscheduled DNA synthesis in aging human fibroblast-like cells (Dell'Orco and Whittle, 1978). At this point, however, a function for polymerase beta in early or late replicative processes cannot be ruled out.…”

Section: Discussionmentioning

confidence: 76%

Reduction of DNA synthesis in aging but still proliferating cells

Collins

Chu

1985

Journal Cellular Physiology

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It is well known that cell proliferation (and hence, DNA synthesis) declines in human diploid fibroblast-like cells with increasing passage number. It is not clear whether D N A synthesis declines in t h e remaining cells that are still actively proliferating. Estimations of cell kinetic parameters permitted extrapolations to be made that reflected the declining numbers of cells still capable of D N A replication. D N A synthesis declined with culture age in intact cells, permeabilized cells, and in the isolated nuclear matrix even when corrected for declining numbers of proliferating cells. With age, DNA polymerase alpha and beta activity in cell lysates declined, but when corrected for the remaining proliferating cells, only polymerase alpha activity declined; D N A polymerase alpha and beta activity bound to the nuclear matrix declined, but when corrected for declining proliferation, no decline was apparent for either enzyme. There was an increase in the number of S1-nuclease sensitive sites and breaks in the parental DNA of the dividing cells in older cultures. It is suggested that in aging cultures, not only does overall DNA synthesis decline owing to decreasing cell proliferation, but also that D N A synthesis declines in t h e remaining proliferating cells, that this decline is not due to decreasing amounts of D N A polymerase bound to the nuclear matrix, and that alterations in D N A structure occur.

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“…The mammary epithelium of the P rat, in a way, is similar to the arrested, non-mitotic population of human diploid fibroblasts (HDF) used by Dell'Orco and Whittle (336) to determine the effect of aging on UDS induced by UV irradiation. The findings of these authors demonstrate that HDF cells which are arrested in a non-mitotic state exhibit a higher level of UDS over normal confluent HDF cells, and this increase is not due to variations in response to UV irradiation or altered precursor pools.…”

Section: (V) Dna Repair By Mammary Epithelium In Primary Culturementioning

confidence: 99%

Differentiation of the mammary gland and susceptibility to carcinogenesis

Russo¹,

Tay²,

Russo³

1982

Breast Cancer Res Tr

562

402

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It has been demonstrated that in humans certain factors such as early menarche, late pregnancy, and nulliparity are associated with a higher risk of developing breast cancer, while early pregnancy acts as a protective factor. Induction of mammary cancer in rats by administration of the chemical carcinogen 7,12-dimethylbenz(a)anthracene reveals that the same factors influencing human breast cancer risk also affect the susceptibility of the rat mammary gland to the chemical carcinogen. Nulliparous rats and rats undergoing pregnancy interruption are more susceptible to developing carcinomas. This fact has been attributed to the incomplete differentiation of the gland at the time of carcinogen administration. Parous rats are resistant to the carcinogenic effect of DMBA, which is explained by the complete development of the gland attained during pregnancy and lactation. This development is manifested by the differentiation of terminal end buds into secretory units, which have a smaller proliferative compartment; the epithelial cells of these secretory units have a longer cell cycle, less avidity for binding DMBA, and possess a more efficient DNA excision repair capacity.

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Unscheduled DNA synthesis in confluent and mitotically arrested populations of aging human diploid fibroblasts

Cited by 29 publications

References 25 publications

Studies of DNA polymerases alpha and beta from cultured human cells in various replicative states

Studies of DNA polymerases alpha and beta from cultured human cells in various replicative states

Reduction of DNA synthesis in aging but still proliferating cells

Differentiation of the mammary gland and susceptibility to carcinogenesis

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