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C S Downes

Publications and source records attributed to C S Downes.

44 records · Page 3Linked to original sources
PubMed1982

Effects of DNA replication inhibitors on UV excision repair in synchronised human cells.

When HeLa cells are irradiated with UV and treated with the DNA synthesis inhibitors hydroxyurea (HU) and 1-beta-D-arabinofuranosylcytosine (ara C), DNA strand breaks accumulate at sites where excision repair of DNA damage has been inhibited after the incision step. This break accumulation occurs in mitotic, G1 and S phase cells. But UV-induced repair synthesis of DNA, as measured by [3H]thymidine incorporation into unreplicated DNA, is not inhibited by HU and ara C in G1 or S phase cells, even though replicative synthesis is virtually abolished. Repair and replication must therefore utilise different DNA precursor pools, or different DNA synthetic systems; and the action of Hu and ara C in causing strand break accumulation may occur at the ligation step of excision repair.

Cytarabine↗
PubMed1982

Cell cycle-dependent regulation of excision repair of UV damage.

The incision step of excision repair of UV-damaged DNA, represented by the accumulation of DNA strand breaks in the presence of hydroxyurea and 1-beta-D-arabinofuranosylcytosine, was measured in cultured cells of Microtus agrestis during quiescence and at different times after release from quiescence. The UV dose-dependent kinetics of enzymic incision change rapidly through the first cell cycle after release, with a maximum potential for enzymic incision and a minimum affinity of the incision system for damage sites occurring in late G1. The potential for incision falls to a lower level as cells approach a randomly proliferating state, whilst the affinity rises. Incision activity declines rapidly after UV irradiation, leaving many damage sites unrepaired; the enhanced survival seen in cells held in quiescence after irradiation is thus partly due to some other repair mode.

Animals↗
PubMed1980

Cell cycle-related variations in UV damage and repair capacity in Chinese hamster (CHO-K1) cells.

UV damage to CHO cell DNA, measured by formation of thymine-containing dimers, increases from mitosis to early S phase. Computer simulation of UV absorption by the DNA of an idealized CHO cell at different stages in the cell cycle resembles the cycle dependence of UV damage. Incision at UV damage sites, measured by the accumulation of breaks in preexisting DNA during 30 minutes' post-irradiation incubation with the DNA synthesis inhibitors 1-beta-D arabinofuranosylcytosine and hydroxyurea, increases from mitosis to interphase. Analysis of the dose dependence of DNA break accumulation indicates that both the affinity of the endonuclease for dimer sites and the maximum enzyme activity at saturating levels of dimers are significantly lower in mitosis than in interphase. The killing of CHO cells by UV is enhanced if repair is temporarily inhibited by are C. The DNA gyrase inhibitor novobiocin prevents UV-induced incision.

Animals↗
PubMed1979

DNA damage in synchronized HeLa cells irradiated with ultraviolet.

The lethal effect of UV radiation of HeLa cells is least in mitosis and greatest in late G1-early S. Photochemical damage to HeLa DNA, as measured by thymine-containing dimer formation and by alkaline sucrose sedimentation, also increases from mitosis towards early S phase. Computer simulations of UV absorption by an idealized HeLa cell at different stages of the cell cycle indicate that changes in damage could be due solely to changes in chromatin geometry. But survival is not exclusively a function of damage.

Cell Division↗
PubMedDate not supplied

Cell-cycle delay is induced in cells of a U937 promonocytic cell line by low-intensity light irradiation at 660 nm.

Visible-light irradiation (VLI) at 660 nm and 11.5 J/cm2 inhibits proliferation of cells of the U937 promonocytic cell line, as monitored by autoradiographical analysis. The S-phase cell population is reduced at 6 h post-radiation treatment. Flow cytometric analysis confirms this, and also shows that light irradiation of cells induces a statistically significant increase in G2/M cells at 6 h post-radiation treatment. It has been postulated that VLI at 660 nm can alter cell-cycle progression by affecting intracellular concentrations of ions, in particular pH and calcium. However, no significant effects of light irradiation on these intracellular ions have been observed. These effects of VLI are not a consequence of radiation-induced DNA strand breaks, therefore events other than direct DNA damage are involved. These findings demonstrate a direct photobiological effect of VLI at 660 nm on the cell cycle, and indicate a previously unsuspected mechanism for the induction of cell-cycle delay that is neither a result of changes in the concentration of intracellular ions nor initiated by DNA strand breaks.

Calcium↗