Effect of caffeine on DNA polymerase I from Escherichia coli studies in vitro and in vivo

Solberg, Knut; Øvrebø, Steinar; Kleppe, Ruth K.; Kleppe, Kjell

doi:10.1016/0027-5107(78)90002-7

Cited by 18 publications

(3 citation statements)

References 30 publications

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“…Experiments with caffeine must, however, be interpreted cautiously because of the wide range of additional effects associated with this substance including modification of a variety of DNA repair functtons (17) and partial suppression of the exonuclease functions of E.coli T)NA polymerase 1 (18). A case in point is the modifying effect of caffeine on the inhibition of DNA synthesis by distamycin A (Figure 3).…”

Section: Effect Of Caffeinementioning

confidence: 99%

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Selective binding of actinomycin D and distamycin A to DNA

Wilkins

1982

Nucl Acids Res

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ABSTRACT.The exact sites at which a number of drugs inhibit the nick translation of DNA by E.coli DNA polymerase-I have been pinpointed. In order to do this, a method has been developed for sequencing double-stranded plasmid DNA from the site of a specifically induced nick. The initial experiments have concentrated on analysis of drug inhibition of nick translation in a 200 nucleotide region near the Eco RI origin of pBR313. Many drugs were found to inhibit nick translation in a highly sequence specific manner.For actinomycin D, significant inhibition occurred at just four sites in the nucleotide sequence under test and only one sequence (pGpCpGpCpGpGp) gave really strong inhibition. Distamycin A gave a different pattern of inhibition with particularly strong stops in just two of the many A-T rich regions in the DNA. Experiments with caffeine suggest that factors in addition to primary sequence are important in determining where major inhibition occurs.

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Section: Effect Of Caffeinementioning

confidence: 99%

“…Just why this phenomenon is observed with distamycin A but not with actinomycin D, nor with caffeine alone, is unclear. However, it should be noted that extensive external binding of caffeine to DNA may occur (19) and that A-T rich regions could be particularly prone to melting (16,18) CONCLUSION.…”

Section: Effect Of Caffeinementioning

confidence: 99%

Selective binding of actinomycin D and distamycin A to DNA

Wilkins

1982

Nucl Acids Res

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“…Alone, caffeine at millimolar concentrations effects cell cycle traverse by prolonging cell transit through GI phase (Burk 1968, O'Neill979, Iliakis & Nusse 1983, induces mutations and chromosomal aberrations (Kihlman 1977), inhibits enzyme systems involved in DNA replication and repair (Tolmach Jones & Busse 1977, Solberg et al 1978, Nolan & Kidder 1979, Selby & Sancar 1990) and causes extensive chromatin condensation (Borodina et al 1979, Musk et af. Alone, caffeine at millimolar concentrations effects cell cycle traverse by prolonging cell transit through GI phase (Burk 1968, O'Neill979, Iliakis & Nusse 1983, induces mutations and chromosomal aberrations (Kihlman 1977), inhibits enzyme systems involved in DNA replication and repair (Tolmach Jones & Busse 1977, Solberg et al 1978, Nolan & Kidder 1979, Selby & Sancar 1990) and causes extensive chromatin condensation (Borodina et al 1979, Musk et af.…”

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confidence: 99%

Caffeine reverses the cytotoxic and cell kinetic effects of Novantrone (mitoxantrone)

1991

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Caffeine is known to potentiate the cytotoxicity of a variety of DNA damaging agents presumably by reducing the ability of the cells to repair potentially lethal lesions. However, in the present study we observe that 5 mM caffeine reverses the cell kinetic and cytotoxic effects of the intercalating drug Novantrone (mitoxantrone) on L1210, HL-60 and CHO cells. Novantrone alone, at a concentration of 20-30 ng/ml, given to cultures for 1 h, inhibits cell growth by about 50% and causes cells to accumulate in S and G2 phase and to enter a higher DNA ploidy level. Treatment of these cell lines with 5 mM caffeine alone for 1 h has a minimal effect on cell proliferation; suppression of cell growth varies from 5 to 10%. Exposure of cells to Novantrone for 1 h in the presence of caffeine results in a significant reduction of the Novantrone effects; the cell growth rate is partially restored (e.g. caffeine reduces suppression of L1210 cell growth from 48 to 83% of control) and in each of the cell lines studied, the Novantrone-induced cell accumulation in S and G2 is abolished. Combined treatment with caffeine and Novantrone also increases the clonogenicity of CHO cells 8.5 times over that seen in cultures treated with Novantrone alone. In contrast to the combined treatment with caffeine + Novantrone, pretreatment of cells with caffeine provides no protection. Likewise, post-treatment with caffeine provides little reversal of growth inhibition and G2 cell accumulation, especially if the post-treatment is delayed in time. The present data, in conjunction with evidence in the literature that caffeine protects cells against the cytotoxic effects of doxorubicin, suggest that caffeine may play a more general role in protecting cells against planar aromatic molecules such as intercalating agents.

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Growth and death of hela cells in the presence of caffeine

Beetham

Tolmach

1982

Journal Cellular Physiology

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Proliferation and death were measured in synchronously growing cultures of HeLa S3 cells during treatment with up to 30 mM caffeine. Changes in the number of colony-forming cells were determined by single-cell plating, while changes in the total number of cells were measured both by electronic counting and by monitoring cell division and physiological death cinemicrographically. At concentrations between 2 and 5 mM, cell killing occurs over several days during which the cells traverse the generation cycle once or a few times before losing colony-forming ability, with consequent proliferation of non-colony-forming cells. This indicates that lethal damage is accumulated with time. Death occurs more rapidly at higher concentrations, without proliferation, the kinetics of inactivation being strongly dependent on the phase of the cycle (cell age) at which treatment is initiated. G1 cells are killed more slowly in 10 mM caffeine than are S cells, but G1 cells respond rapidly to 20 mM caffeine, suggesting the inception of an additional mode of killing. The incidence of sister-cell fusion increases with increasing caffeine concentration above 1 mM. On addition of 10 mM caffeine to a culture prepared from collected mitotic cells, the cells undergo a transient rounding and then respread after several hours; with 20 mM, they never respread. The generation cycle is prolonged in a concentration-dependent fashion, as is the duration of G1; the generation time is doubled in 5-6 mM caffeine. G2 and M are also prolonged at concentrations above 3 mM, but S is not prolonged even by 10 mM caffeine.

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Effect of caffeine on DNA polymerase I from Escherichia coli studies in vitro and in vivo

Cited by 18 publications

References 30 publications

Selective binding of actinomycin D and distamycin A to DNA

Selective binding of actinomycin D and distamycin A to DNA

Caffeine reverses the cytotoxic and cell kinetic effects of Novantrone (mitoxantrone)

Growth and death of hela cells in the presence of caffeine

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