The Interaction of Caffeine with Ultra-violet-light-irradiated DNA

Domon, M.; Barton, Beverly E.; Porte, A. L.; Rauth, Andrew M.

doi:10.1080/09553007014550481

Cited by 91 publications

(25 citation statements)

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“…the DNA structure contains a single-stranded region of this length, where theophylline can bind, thereby inhibiting the enzyme systems. This mechanism is similar to that proposed for caffeine [26,22].…”

Section: Model For Repair With One-enzyme Systemsupporting

confidence: 58%

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Post‐Replication Repair of DNA in Ultraviolet‐Irradiated Mammalian Cells

Lehmann

Kirk-Bell

1972

European Journal of Biochemistry

129

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Ultraviolet light produces pyrimidine dimers in cellular DNA. I n mouse cell lines the great majority of these pyrimidine dimers are not excised, but remain in high molecular weight DNA. Hence the DNA used as template for DNA synthesis in the first generation after ultraviolet irradiation must contain such dimers. I n two mouse cell lines (L5178Y and 3T3), alkaline sucrose sedimentation studies showed that the DNA pulse-labelled shortly after irradiation contained gaps, which by analogy with the situation in Escherichia coli, are presumed to be opposite the pyrimidine dimers. In contrast such gaps could not be detected in DNA pulse-labelled several hours after irradiation, despite the fact that dimers must have been present on the template strands. A possible explanation is that gaps were still being formed, but were filled in rapidly and were therefore not detected. This hypothesis was tested as follows. Either 1 or 8 h after ultraviolet irradiation cells were pulse-labelled in the presence of theophylline. This purine inhibits the filling in of gaps presumably by binding to the DNA in the gap. Even in the presence of theophylline, the late-synthesized DNA was considerably larger than the early-synthesized DNA. This suggests that a t late times after irradiation, gaps were either not formed a t all opposite the dimers, or were so transient that theophylline could not bind and inhibit their filling in. A model for synthesis of DNA on templates containing pyrimidine h e r s in mammalian cells, based on these findings and other recent results, is discussed.Pyrimidine dimers are thought to be the principal ultraviolet-light-induced lesions in cellular DNA. Many organisms including human cells [l] can excise these dimers from their DNA. Cells from human patients carrying the disease Xeroderma Pigmentosum and also many rodent cells have very little or no ability to excise these dimers [2-51. Nevertheless all these cells can survive ultraviolet doses producing a t least lo5 pyrimidine dimers per cell and all mammalian cells studied appear to be able to replicate DNA containing pyrimidine dimers. Synthesis on templates containing pyrimidine dimers occurs by a process termed post-replication repair (recombination repair), similar to that first discovered by Rupp and Howard-Flanders in an excision-defective strain of Escherichia coli [6]. I n mouse L517SY cells [7], as in E. coli [S], a gap of about 1000 nucleotides is left opposite the dimer during replication, and this gap is subsequently filled in. Post-replication repair has been observed in Chinese hamster cells 19,101 and in mouse L517SY cells [11,7]; the details of the gap-filling process in mouse L5178Y cells have been described in an earlier paper [7]. Recently Chiu and Rauth [12] using L cells could only detect such gaps in the daughter DNA strands after relatively high ultraviolet doses. If the correct controls were done, taking into account labelling artefacts [13,14], gaps could not he detected after lower doses.During the Grst generation after ultraviolet i...

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Section: Model For Repair With One-enzyme Systemsupporting

confidence: 58%

“…Theophylline differs structurally from caffeine only by the absence of one methyl group. Caffeine has been shown to bind to single-stranded DNA but not to double-stranded DNA [25,26]. It is assumed that theophylline acts in a similar manner.…”

Section: Model For Repair With One-enzyme Systemmentioning

confidence: 99%

Post‐Replication Repair of DNA in Ultraviolet‐Irradiated Mammalian Cells

Lehmann

Kirk-Bell

1972

European Journal of Biochemistry

129

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“…KUHLMANN et al (1968) have suggested a similar mechanism for the production of aberrations by caffeine. Whereas such a mechanism is quite compatible with chemical data on the effects of alkylating agents on DNA (for discussion and references, see KIHLMAN 1971b) it does not agree well with the data on the interaction between caffeine and DNA (Ts 'o et al 1962;Ts'o and Lu 1964;DOMON et al 1970).…”

Section: Discussionmentioning

confidence: 56%

“…That the first mechanism probably is the more specific one is indicated by: ( I ) the type of aberration produced (exchanges), (2) the ATP dependence, (3) the unusual relationship between effect and temperature (effect increasing with decreasing temperature) and, (4) the fact that the effectiveness of the methylated oxypurines is strongly influenced by variations in their molecular structure (see also KIHLMAN 1952). In the first article in this series (KIHLMAN et al 1971), it was suggested that the exchange-process induced by methylated oxypurines in root-tip cells is a result of the ability of these substances to combine with singlestranded DNA (Ts'o et al 1962;Ts'o and Lu 1964;DOMON et al 1970). More details about the proposed mechanism for production of exchanges can be found in the fore-mentioned paper (KIHLMAN et al 1971).…”

Section: Discussionmentioning

confidence: 99%

Caffeine, caffeine derivatives and chromosomal aberrations

Ba¹,

Sturelid²,

Norlén³

et al. 2009

Hereditas

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The effects ofcaffeine, 8-ethoxycaffeine(EOC), and 6-methylcoumarin (6-MC) on chromosome structure were studied with root tips of Alliumproliferum (Egyptian or tree onion) and cell cultures of the Chinese hamster as experimental materials. The results indicate that the three substances produce chromosomal aberrations by similar mechanisms.Root tips were treated at 20°C. The majority of the aberrations were obtained in cells exposed during late G, and prophase, and "subchromatid" and chromatid exchanges predominated among the aberrations produced. The effect was dependent on the ATP concentration in the roots. Very few aberrations were produced when the generation of ATP was suppressed by anoxia or by sodium azide. On a molar basis, EOC was approximately four times more active than caffeine.When treated at 37"C, Chinese hamster cells were affected during the interphase period of DNA synthesis (the S-phase). The effect consisted of a pronounced fragmentation of chromatids. The aberrations were produced independently of the concentration of ATP in the cells. At 37"C, caffeine and EOC were about equally effective as chromosome-breaking agents.When treated at 17"C, Chinese hamster cells responded to caffeine and EOC in very much the same way as did plant cells. The majority of the aberrations were produced in cells treated during prophase or G,. About half of these aberrations (gaps excluded) were "subchromatid" and chromatid exchanges. However, the frequencies of chromatid breaks and the degree of incompleteness of the exchanges were considerably higher in hamster cells than in Allium root tips. EOC was considerably more effective than caffeine. The effect was dependent on ATP.

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“…Caffeine is an effective repair inhibitor in phages (31), bacteria (19, 23 and review 35), yeasts (1, 6-8, 18, 25, 26) and mammalian cells (e.g., 27), as shown by the marked decrease of survivors when cells are exposed to caffeine immediately after U V-irradiation This lethal-enhancing effect of caffeine is explained by its binding to denatured regions of DNA (5,37) and probably by consequent inhibition of the action of enzymes responsible for repair of DNA (see review 20) This study was designed to investigate dark reactivation in human mycoplasma cells with the aid of caffeine The results indicate that Mycoplasma buccale possesses the function of dark reactivation.…”

mentioning

confidence: 99%

UV Survival of Human Mycoplasmas: Evidence of Dark Reactivation in Mycoplasma buccale

Aoki

Ito

Watanabe

1979

Microbiology and Immunology

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The inactivation by ultraviolet (UV) light irradiation of mycoplasma cells of five human strains was monitored by investigating the colony-forming ability. The survival curves of five strains tested indicated that the cells of Mycoplasma buccale only are single and homogenously susceptible to UV light. The effect of the repair inhibitor, caffeine, on the colony-forming ability of UV-irradiated cells was investigated with Al. buccale because of its homogenous susceptibility to UV light. The colony formation of irradiated cells was markedly depressed by post-irradiation treatment with caffeine at concentrations that had little or no effect on the colony formation of unirradiated cells. The colony-forming units (CFU) of UV-irradiated cells which were kept in broth without caffeine in the dark increased without a lag as the time in the dark increased. The colony-forming ability of the irradiated cells completely recovered after 3 hr in the dark. However, when irradiated cells were kept in the presence of caffeine, no increase in their CFU was observed. The mode of action of caffeine on UV-irradiated cells closely resembles that described for other organisms which possess dark reactivation systems for UV-induced damage in deoxyribonucleic acid (DNA). Thus, the results obtained provide evidence for the existence of a dark repair function in M. buccale.

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The Interaction of Caffeine with Ultra-violet-light-irradiated DNA

Cited by 91 publications

References 1 publication

Post‐Replication Repair of DNA in Ultraviolet‐Irradiated Mammalian Cells

Post‐Replication Repair of DNA in Ultraviolet‐Irradiated Mammalian Cells

Caffeine, caffeine derivatives and chromosomal aberrations

UV Survival of Human Mycoplasmas: Evidence of Dark Reactivation in Mycoplasma buccale

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