Growth and death of hela cells in the presence of caffeine

Beetham, Karen L.; Tolmach, L. J.

doi:10.1002/jcp.1041130306

Cited by 10 publications

(10 citation statements)

References 37 publications

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“…It was found that with 5 mM caffeine, 0.5-5 mM HOU give maximal killing; 0.1 mM is less effective. With 1 mM HOU, 5 and 10 mM caffeine are maximally effective, 3 or 20 mM less so, the latter presumably because of its large toxicity (by itselfl to G1 cells (Beetham and Tolmach, 1982b). Similar though less extensive measurements of the synergistic effect with cells treated in S indicate general agreement with the results of GI-initiated exposures.…”

Section: Age Dependencesupporting

confidence: 71%

“…It has also been found to increase unpredictably the rate of DNA synthesis Painter, 1980). In addition, at concentrations between 5 and 15 mM, caffeine kills our line of HeLa cells if they are in S, but at higher concentrations it kills cells in G1 as well (Beetham and Tolmach, 1982b). It also induces mutations and chromosome aberrations (see Kihlman, 1977).…”

mentioning

confidence: 99%

“…The cytotoxicity of caffeine has received comparatively little study. At millimolar concentrations, it slows cell progression through GI, G2, and M, but apparently not through S (Beetham and Tolmach, 1982b), although it inhibits the incorporation of exogenous thymidine into DNA (Lehmann and Kirk-Bell, 1974). It has also been found to increase unpredictably the rate of DNA synthesis Painter, 1980).…”

mentioning

confidence: 99%

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Synergistic killing of Hela cells by hydroxyurea and caffeine

Beetham

Busse

Tolmach

1983

Journal Cellular Physiology

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Synchronous populations of HeLa S3 cells suffer synergistic killing during S phase in the presence of 0.5-5 mM hydroxyurea together with 5-10 mM caffeine. Both the rate and the extent of killing are greater than expected for independent action of the two drugs. Only simultaneous treatment is effective. The dependence of the synergistic killing on cell age resembles the age dependence for killing by hydroxyurea alone (greater than 3 mM), but not that by high concentrations of caffeine. In addition, rapid killing occurs if caffeine is added to cultures that have been incubated in the presence of hydroxyurea from early G1 and are blocked at the beginning of S, although such cells are killed only slowly on continued incubation in greater than or equal to 10 mM hydroxyurea alone. Furthermore, cells that are incubated with the two drugs from early G1 begin to undergo synergistic killing at about 12 h after mitotic collection, but they do not commence DNA replication for another 2-3 h if the drugs are removed. It is concluded that cells that have reached a point in the cycle identical with or close to the end of G1 are sensitive to the combination whether or not they are able to synthesize DNA, and whether or not they are sensitive to hydroxyurea alone. A tentative model is proposed: hydroxyurea is postulated to kill cells by interacting with sites of replication in DNA, and the synergism is attributed to the extra replication points that caffeine is known to induce.

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Section: Age Dependencesupporting

confidence: 71%

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confidence: 99%

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confidence: 99%

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Synergistic killing of Hela cells by hydroxyurea and caffeine

Beetham

Busse

Tolmach

1983

Journal Cellular Physiology

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“…Caffeine has long been known to induce a G1 delay in mammalian cells [65][66][67], and we showed that caffeineinduced ~75% inhibition of G1/S progression in diploid human fibroblast strains. ATM and p53 were not required as AT cells and cells expressing HPV16E6 to inactivate p53 also arrested in G1 when incubated in caffeine.…”

Section: Discussionmentioning

confidence: 72%

Caffeine and human DNA metabolism: the magic and the mystery

Kaufmann

Heffernan

Beaulieu

et al. 2003

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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The ability of caffeine to reverse cell cycle checkpoint function and enhance genotoxicity after DNA damage was examined in telomerase-expressing human fibroblasts. Caffeine reversed the ATM-dependent S and G2 checkpoint responses to DNA damage induced by ionizing radiation (IR), as well as the ATR-and Chk1-dependent S checkpoint response to ultraviolet radiation (UVC). Remarkably, under conditions in which IR-induced G2 delay was reversed by caffeine, IR-induced G1 arrest was not. Incubation in caffeine did not increase the percentage of cells entering the S phase 6-8 h after irradiation; ATM-dependent phosphorylation of p53 and transactivation of p21 Cip1/Waf1 post-IR were resistant to caffeine. Caffeine alone induced a concentration-and time-dependent inhibition of DNA synthesis. It inhibited the entry of human fibroblasts into S phase by 70-80% regardless of the presence or absence of wildtype ATM or p53. Caffeine also enhanced the inhibition of cell proliferation induced by UVC in XP variant fibroblasts. This effect was reversed by expression of DNA polymerase η, indicating that translesion synthesis of UVC-induced pyrimidine dimers by DNA pol η protects human fibroblasts against UVC genotoxic effects even when other DNA repair functions are compromised by caffeine.

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“…While caffeineinduced perturbations in mitosis and cell division are well documented (e.g. Kihlman, 1977;Beetham & Tolmach, 1982), and while caffeine may inhibit cell division in C. elegans, the developmental biology of this organism indicates this hypothesis to be untenable. Specifically, the increase in size throughout development is due largely to increase in cell size rather than cell number.…”

Section: Discussionmentioning

confidence: 97%