New Evidence Concerning the Molecular Basis of the Restorative Effect of DNA in Cultured Mammalian Cells

Petrović, Danilo; Ferle-Vidović, Ana; Habazin, Vlasta; Vuković, Biserka

doi:10.1080/09553007014551061

Cited by 10 publications

(5 citation statements)

References 12 publications

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“…Subsequently, more recent work has focused on the effects of nucleoside and nucleotide pools on cell or whole organism survival. Petrovic et al [12] were able to demonstrate that exogenous DNA would provide increased survival of mouse L-V166 cells to ionizing radiation. This was thought to be due to an increase in the free nucleotide and nucleoside pools.…”

Section: Resultsmentioning

confidence: 99%

“…This work was later confirmed by Horikawa et al [8] using cellular fractions and deoxyribonucleic acid. More recently, workers demonstrated that this protective effect of DNA is seen in other cell culture models [9][10][11][12]. However, these authors used undamaged DNA and did not specifically investigate the effects of damaged DNA on protecting cells.…”

Section: Introductionmentioning

confidence: 99%

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The Cytoprotective Effects of Exogenous DNA Fragments

Mammone

Ingrassia²,

Gan³

et al. 2001

Skin Pharmacol Physiol

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Ultraviolet irradiation of normal human keratinocytes induces a cytotoxic effect. The chromophore for this effect is believed to be genomic DNA. However, DNA damage is known to be repaired in UVB irradiated keratinocytes. The trigger for this DNA repair is potentially damaged DNA itself. To test the hypothesis that damaged DNA can induce the host cell’s own DNA repair mechanism, we treated the keratinocytes with the damaged DNA and evaluated its cytoprotective effects. We have observed that fragmented calf thymus DNA irradiated and damaged with a UVC light can induce a protective effect in cultured human keratinocytes. Keratinocytes treated with UVC damaged DNA fragments are less susceptible to UVB irradiation-induced cell death as measured by neutral red uptake. Unirradiated exogenous DNA did not induce this protective effect. Similar protective effects can be seen with irradiated salmon sperm DNA. UVC damaged DNA fragments induced 60% increase in protection in human HaCaT keratinocyte in culture to the cell death induced by UVB. Similar protection was observed with UVC irradiated oligothymidylic acid (dT3-dT5) which increased the survival of human HaCaT keratinocytes after UVB irradiated by 50%. Isolated mononucleotides, irradiated or not, do not increase UVB survivability. Cellular DNA synthesis was greatly inhibited by UVB, becoming undetectable at 40 mJ/cm². Exogenous treatment with damaged fragments causes immediate and significant inhibition of total cellular DNA synthesis. This inhibition was dose dependent. Cells that undergo damage to their DNA are known to inhibit endogenous DNA synthesis via p53 suppressor gene activation. This is believed to allow them sufficient time to repair the host DNA. The cellular response to exogenous damaged DNA may be a similar mechanism.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Cytoprotective Effects of Exogenous DNA Fragments

Mammone

Ingrassia²,

Gan³

et al. 2001

Skin Pharmacol Physiol

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“…In vitro, an apoptotic cell may persist in the characteristic structure for an hour or two (Wyllie, 1992). The duration of mitosis of mouse fibroblasts grown in culture has been estimated to be approximately an hour (Petrovic et al, 1970). The proportions of mitotic and apoptotic cells in a range of experimental tumors are reported by Sarraf and Bowen (1988).…”

Section: -mentioning

confidence: 99%

Mitotic activity, apoptosis and TRPM‐2 mRNA expression in dmba‐induced rat mammary carcinoma treated with anti‐estrogen toremifene

Huovinen

Wärri

Collan

1993

Intl Journal of Cancer

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Anti-estrogen toremifene inhibits growth of the 7,12-dimethylbenz(a)anthracene(DMBA)-induced rat mammary carcinoma. The changes in proliferation and cell death were studied in detail. Proliferation was measured by counting mitotic figures in histologic sections, expressed by volume-corrected mitotic index (M/V INDEX). Respective volume corrected apoptotic index (A/V INDEX) was measured by counting apoptotic nuclei in the same sections. The presence of apoptotic cells was confirmed by transmission electron microscopy. In the untreated tumors, both mitosis and apoptosis were frequent. In the toremifene-treated tumors, the mean M/V INDEX was about half of the mean M/V INDEX in the untreated control tumors. The mean A/V INDEX in the toremifene-treated tumors was about 3/4 of the mean A/V INDEX in the controls. In toremifene-treated tumors, A/V INDEX was strongly correlated with TRPM-2-gene expression, which was also enhanced when compared with the controls. TRPM-2 gene has been associated with programmed cell death induced by hormonal ablation in prostate- and breast-cancer cells. No such correlation was seen in control tumors. These findings suggest that, in the DMBA-tumor model, toremifene affects the cell turnover by inhibiting mitotic activity and modifying abundant spontaneous apoptosis. In this model, the inhibition of tumor growth results mostly from reduction of mitotic activity.

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“…The phenomenon of such nucleoside effect is ascribed to repair-promoting events in S-phase cells (Petrovi6 et al, 1970).…”

Section: Experiments With Cyclotron-produced Neutronsmentioning

confidence: 99%

Absence of AET protection against fast neutrons: Cellular effects

Ferle-Vidović

Petrović

Vidić

et al. 1981

Radiat Environ Biophys

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A series of experiments has been undertaken in order to test the biological properties of neutrons produced in the cyclotron of the Institute "Ruder Bosković" (IRB) in Zagreb. Protective effect of AET (2-amino ethylisothiuronium bromide hydrobromide) on survival of L cells irradiated by fast neutrons generated in the IRB cyclotron were studied by employing the single cell clonal growth method. For comparison the protective effect of AET after gamma irradiation has also been studied. The most important findings that have emerged from these experiments can be summarized as follows: (1) Protective effect of AET was present after gamma irradiation only. (2) The degree of protection was dependent on AET concentration in the growth medium. (3) No protective effect was found after neutron irradiation. These findings are in agreement with the generally less efficient protection of this compounds after high-LET irradiation.

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New Evidence Concerning the Molecular Basis of the Restorative Effect of DNA in Cultured Mammalian Cells

Cited by 10 publications

References 12 publications

The Cytoprotective Effects of Exogenous DNA Fragments

The Cytoprotective Effects of Exogenous DNA Fragments

Mitotic activity, apoptosis and TRPM‐2 mRNA expression in dmba‐induced rat mammary carcinoma treated with anti‐estrogen toremifene

Absence of AET protection against fast neutrons: Cellular effects

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