Differential effects of actinomycin D and puromycin on the release of interferon induced by double stranded RNA.
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Biomedical subjects
T G Rossman
Publications and source records attributed to T G Rossman.
Influence of the rate of cell growth and cell density on interferon action in chick embryo cells.
Chick embryo cells became more sensitive to the action of interferon the longer they remained in culture. This phenomenon was found even before confluency had been reached. The relative insensitivity of newly seeded cells was not due to a loss of receptors. Cells synthesizing deoxyribonucleic acid (DNA) at a high rate were less sensitive to interferon action than cells synthesizing DNA at a low rate, but the inhibition of DNA synthesis had no effect on interferon action. An increase in the number of cells used for seeding resulted in an earlier appearance of increased sensitivity to interferon action. These results are discussed in relation to the induction process in animal cells.
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Mechanism of comutagenesis of sodium arsenite with n-methyl-n-nitrosourea.
Arsenic compounds are known carcinogens. Although many carcinogens are also mutagens, we have previously shown that sodium arsenite is not mutagenic at either the Na+/K+ ATPase or hprt locus in Chinese hamster V79 cells. It can, however, enhance UV-mutagenesis. We now confirm the nonmutagenicity of sodium arsenite in line G12, a pSV2gpt-transformed V79 (hprt-) cell line, which is able to detect multilocus deletions in addition to point mutations and small deletions. The lack of arsenic mutagenicity has led to studies emphasizing its comutagenicity. Sodium arsenite at relatively nontoxic concentrations (5 microM for 24 h or 10 microM for 3 h) is comutagenic with N-methyl-N-nitrosourea (MMU) at the hprt locus in V79 cells. Using a nick translation assay, which measures DNA strand breaks by incorporating radioactive deoxyribonucleoside monophosphate at their 3'OH ends in permeabilized cells, we found that much more incorporation was seen in cells treated with MNU (4 mM, 15 min) followed by 3-h incubation with 10 microM sodium arsenite compared with cells exposed to the same MNU treatment followed by 3-h incubation without sodium arsenite. This result shows that in the presence of arsenite, strand breaks resulting from MNU or its repair accumulate over a 3-h period. We suggest that the repair of MNU-induced DNA lesions may be inhibited by arsenite either by affecting the incorporation of dNMPs into the MNU-damaged DNA template or by interfering with the ligation step.
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On the mechanism of the comutagenic effect of Cu(II) with ultraviolet light.
Although CuCl2 alone is not mutagenic in E. coli or in Chinese hamster cells, exposure of E. coli to CuCl2 during UV-irradiation causes enhancement of UV-mutagenesis. The mechanism for this comutagenic effect appears to be owing to increased DNA damage by the combined treatment of UV and Cu(II) compared with UV or Cu(II) alone. Using a sequencing gel approach, UV alone is found to cause a particular pattern of alkali-labile sites, whereas CuCl2 alone caused few such sites. The combined action of UV + CuCl2 greatly increased the amount of sites over that of UV alone, and caused a change in their pattern. In the presence of high NaCl concentrations, however, Cu(II) is able to induce DNA damage. This latter effect is most likely owing to the formation of hypochlorite ion. The hypothesis that the comutagenic effect of Cu(II) plus UV might be owing to hydroxyl radical formed via a Fenton reaction involving Cu(II) and UV-generated H2O2 was not supported, since no H2O2 is detectable in aqueous medium after UV irradiation, and catalase did not block the DNA damage. These results favor the hypothesis that UV-irradiation of Cu(II) causes a photoactivation, enabling it to generate free radicals, perhaps by reacting with dissolved oxygen.
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Inhibition of DNA synthesis is not sufficient to cause mutagenesis in Chinese hamster cells.
Experiments were designed to test whether the inhibition of DNA synthesis in Chinese hamster V79 cells would result in increased mutagenesis by a mechanism similar to "SOS repair" in E. coli. Treatment of cells for 16 hours with excess of the deoxynucleosides TdR, UdR, AdR and GdR was mutagenic, whereas treatment with hydroxyurea demonstrated no mutagenic effect. The mutagenicity of TdR could be reversed by the addition of CdR. In E. coli, inhibition of DNA synthesis by a short exposure to hydroxyurea resulted in the induction of lambda prophage and increased mutagenesis. These results show that whereas the presence of a stalled replication fork in E. coli can result in mutagenesis via induction of the "SOS system", the same phenomenon does not seem to occur in Chinese hamster V79 cells. The mutagenic mechanism of high concentrations of deoxynucleosides in Chinese hamster V79 cells is likely to be due to replication errors which result from alterations in deoxynucleotide pools.
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