Abstract
Caffeine is a compound that can exert physiological–beneficial effects in the organism. Nevertheless, there are controversies about its protective-antioxidant and/or its negative genotoxic effect. To abound on the analysis of the possible genotoxic/antioxidant effect of caffeine, we used as research model the yeast Yarrowia lipolytica parental strain, and mutant strains (∆rad52 and ∆ku80), which are deficient in the DNA repair mechanisms. Caffeine (5 mM) showed a cytostatic effect on all strains, but after 72 h of incubation the parental and ∆ku80 strains were able to recover of this inhibitory effect on growth, whereas ∆rad52 was unable to recover. When cells were pre-incubated with caffeine and H2O2 or incubated with a mixture of both agents, a higher inhibitory effect on growth of mutant strains was observed and this effect was noticeably greater for the Δrad52 strain. The toxic effect of caffeine appears to be through a mechanism of DNA damage (genotoxic effect) that involves DSB generation since, in all tested conditions, the growth of Δrad52 strain (cells deficient in HR DNA repair mechanism) was more severely affected.
References
Abreu RV, Silva-Oliveira EM, Moraes MFD, Pereira GS, Moraes-Santos T (2011) Chronic coffee and caffeine ingestion effects on the cognitive function and antioxidant system of rat brains. Pharmacol Biochem Behav 99(4):659–664
Alao JP, Sjölander JJ, Baar J, Özbaki-Yagan N, Kakoschky B, Sunnerhagen P (2014) Caffeine stabilizes Cdc25 independently of Rad3 in Schizosaccharomyces pombe contributing to checkpoint override. Mol Microbiol 92(4):777–796
Andaluz E, Ciudad T, Gomez-Raja J, Calderone R, Larriba G (2006) Rad52 depletion in Candida albicans triggers both the DNA-damage checkpoint and filamentation accompanied by but independent of expression of hypha-specific genes. Mol Microbiol 59:1452–1472
Asaad NA, Zeng ZC, Guan J, Thacker J, Iliakis G (2000) Homologous recombination as a potential target for caffeine radiosensitization in mammalian cells: reduced caffeine radiosensitization in XRCC2 and XRCC3 mutants. Oncogene 19(50):5788–5800
Ashengroph M, Ababaf S (2014) Use of Taguchi methodology to enhance the yield of caffeine removal with growing cultures of Pseudomonas pseudoalcaligenes. Iran J Microbiol 6(6):428–436
Azam S, Hadi N, Khan NU, Hadi SM (2003) Antioxidant and prooxidant properties of caffeine, theobromine and xanthine. Med Sci Monit 9(9):325–330
Benkö Z, Sipiczki M (1993) Caffeine tolerance in Schizosaccharomyces pombe: physiological adaptation and interaction with theophylline. Can J Microbiol 39(5):551–554
Block W, Merkle D, Meek K, Lees-Miller S (2004) Selective inhibition of the DNA-dependent protein kinase (DNA-PK) by the radiosensitizing agent caffeine. Nucleic Acids Res 32(6):1967–1972
Bode AM, Dong Z (2007) The enigmatic effects of caffeine in cell cycle and cancer. Cancer Lett 247(1):26–39
Brezova V, Slebdova A, Stasko A (2009) Coffee as a source of antioxidants: an EPR study. Food Chem 114:859–868
Calvo IA, Gabrielli N, Iglesias I, García S, Hoe K, Kim D, Sansó M, Zuin A, Pérez P, Ayté J, Hidalgo E (2009) Genome-wide screen of genes required for caffeine tolerance in fission yeast. PLoS One 4(8):e66
Campos-Góngora E, Andaluz E, Bellido A, Ruiz-Herrera J, Larriba G (2013) The RAD52 ortholog of Yarrowia lipolytica is essential for nuclear integrity and DNA repair. FEMS Yeast Res 13(5):441–452
Ceccaldi R, Rondinelli B, D’Andrea AD (2016) Repair pathway choices and consequences at the double-strand break. Trends Cell Biol 26(1):52–64
Chattopadhyay D, Somaiah A, Raghunathan D, Thirumurugan K (2014) Dichotomous effect of caffeine, curcumin, and naringenin on genomic DNA of normal and diabetic subjects. Scientifica (Cairo) 2014:649261
Ciudad T, Andaluz E, Steinberg-Neifach O, Lue NF, Gow NA, Calderone RA, Larriba G (2004) Homologous recombination in Candida albicans: role of CaRad52p in DNA repair, integration of linear DNA fragments and telomere length. Mol Microbiol 53(4):1177–1194. https://doi.org/10.1111/j.1365-2958.2004.04197.x
Dash SS, Gummadi SN (2006) Catabolic pathways and biotechnological applications of microbial caffeine degradation. Biotech Lett 28(24):1993–2002
Deplanque G, Céraline J, Lapouge G, Dufour P, Bergerat J, Klein-Soyer C (2004) Conflicting effects of caffeine on apoptosis and clonogenic survival of human K1 thyroid carcinoma cell lines with different p53 status after exposure to cisplatin or UVc irradiation. Biochem Biophys Res Comm 314(4):1100–1106
Devasagayam TP, Kamat JP, Mohan H, Kesavan PC (1996) Caffeine as an antioxidant: inhibition of lipid peroxidation induced by reactive oxygen species. Biochim Biophys Acta 1282(1):63–70
Ferre S (2008) An update in the mechanisms of the psychostimulant effects of caffeine. J Neurochem 105:1067–1079
Finn K, Lowndes N, Grenon M (2012) Eukaryotic DNA damage checkpoint activation in response to double-strand breaks. Cel Mol Life Sci 69:1447–1473
Fisone G, Borgkvist A, Usiello A (2004) Caffeine as a psychomotor stimulant: mechanism of action. Cel Mol Life Sci 67:857–872
Gorbunova V, Seluanov A (2016) DNA double strand break repair, aging and the chromatin connection. Mutat Res 788:2–6
Gordillo-Bastidas D, Oceguera-Contreras E, Salazar-Montes A, González-Cuevas J, Hernández-Ortega LD, Armendáriz-Borunda J (2013) Nrf2 and Snail-1 in the prevention of experimental liver fibrosis by caffeine. World J Gastroenterol 19(47):9020–9033
Gülcin I (2008) In vitro prooxidant effect of caffeine. J Enz Inhib Med Chem 23(1):149–152
Gutiérrez-Sánchez G, Roussos S, Augur C (2013) Effect of caffeine concentration on biomass production, caffeine degradation, and morphology of Aspergillus Tamarii. Folia Microbiol (Praha) 58(3):195–200
Han W, Ming M, He YY (2011) Caffeine promotes ultraviolet B-induced apoptosis in human keratinocytes without complete DNA repair. J Biol Chem 286(26):22825–22832
Hapeta P, Rakicka M, Dulermo R, Gamboa-Meléndez H, Cruz-Le Coq AM, Nicaud JM, Lazar Z (2017) Transforming sugars into fat—lipid biosynthesis using different sugars in Yarrowia lipolytica. Yeast 34(7):293–304
Heckman M, Weil J, González de Mejía E (2010) Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. J Food Sci 75(3):R77–R87
Hinz JM (2010) Role of homologous recombination in DNA interstrand crosslink repair. Environ Mol Mutagen 51(6):582–603
Kretzschmar A, Otto C, Holz M, Werner S, Hübner L, Barth G (2013) Increased homologous integration frequency in Yarrowia lipolytica strains defective in non-homologous end-joining. Curr Genet 59(1–2):63–72
Lee C (2000) Antioxidant ability of caffeine and its metabolites based on the study of oxygen radical absorbing capacity and inhibition of LDL peroxidation. Clin Chim Acta 295(1–2):141–154
León-Carmona JR, Galano A (2011) Is caffeine a good scavenger of oxygenated free radicals? J Phys Chem B 115(15):4538–4546
Mercer J, Gray K, Figg N, Kumar S, Bennett M (2012) The methyl xanthine caffeine inhibits DNA damage signaling and reactive species and reduces atherosclerosis in ApoE (−/−) mice. Arterioscler Thromb Vasc Biol 32(10):2461–2467
Metro D, Cernaro V, Santoro D, Papa M, Buemi M, Benvenga S, Manasseri L (2017) Beneficial effects of oral pure caffeine on oxidative stress. J Clin Transl Endocrinol 10:22–27
Nicaud JM (2012) Yarrowia lipolytica. Yeast 29(10):409–418
Ogawa H, Ueki N (2007) Clinical importance of caffeine dependence and abuse. Psychiatry Clin Neurosci 61(3):263–268
Prasanthi J, Dasari B, Marwarha G, Larson T, Chen X, Geiger J, Ghribi O (2010) Caffeine protects against oxidative stress and Alzheimer’s disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet. Free Radical Biol Med 49(7):1212–1220
Sabisz M, Skladanowski A (2008) Modulation of cellular response to anticancer treatment by caffeine: inhibition of cell cycle checkpoints, DNA repair and more. Current Pharm Biotech 9(4):325–336
Salmones D, Mata G, Waliszewski KN (2005) Comparative culturing of Pleurotus spp. on coffee pulp and wheat straw: biomass production and substrate biodegradation. Bioresour Technol 96(5):537–544
Salomone F, Galvano F, Li Volti G (2017) Molecular bases underlying the hepatoprotective effects of coffee. Nutrients 9(1):85
Schwartz C, Frogue K, Ramesh A, Misa J, Wheeldon I (2017) CRISPRi repression of nonhomologous end-joining for enhanced genome engineering via homologous recombination in Yarrowia lipolytica. Biotechnol Bioeng 114(12):2896–2906
Sherman F (2002) Getting started with yeast. Methods Enzymol 350:3–41
Shimizu I, Yoshida Y, Suda M, Minamino T (2014) DNA damage response and metabolic disease. Cell Metab 20(6):967–977
Stein A, Kalifa L, Sia EA (2015) Members of the RAD52 epistasis group contribute to mitochondrial homologous recombination and double-strand break repair in Saccharomyces cerevisiae. PLoS Genet 11(11):e1005664
Summers RM, Mohanty SK, Gopishetty S, Subramanian M (2015) Genetic characterization of caffeine degradation by bacteria and its potential applications. Microb Biotechnol 8(3):369–378
Symington LS (2002) Role of RAD52 epistasis group genes in homologous recombination and double-strand break repair. Microbiol Mol Biol Rev 66(4):630–670
Tiwari KK, Chu C, Couroucli X, Moorthy B, Lingappan K (2014) Differential concentration-specific effects of caffeine on cell viability, oxidative stress, and cell cycle in pulmonary oxygen toxicity in vitro. Biochem Biophys Res Commun 450(4):1345–1350
Varma S, Hegde K (2010) Prevention of oxidative damage to lens by caffeine. J Ocul Pharmacol Ther 26(1):73–77
Verbeke J, Beopoulos A, Nicaud JM (2013) Efficient homologous recombination with short length flanking fragments in Ku70 deficient Yarrowia lipolytica strains. Biotechnol Lett 35(4):571–576
Wang H, Boecker W, Wang H, Wang X, Guan J, Thompson LH, Nickoloff J, Iliakis G (2004) Caffeine inhibits homology-directed repair of I-SceI-induced DNA double-strand breaks. Oncogene 23(3):824–834
Funding
This work was supported in part by National Council of Science and Technology of México (CONACYT) with a fellowship to CAQG (Grant No. 581423), and the UANL-PAICYT Program under Grant No. CS1166-11.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Communicated by Erko Stackebrandt.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Quiñones-González, C.A., Arredondo-Mendoza, G.I., Jiménez-Salas, Z. et al. Genotoxic effect of caffeine in Yarrowia lipolytica cells deficient in DNA repair mechanisms. Arch Microbiol 201, 991–998 (2019). https://doi.org/10.1007/s00203-019-01658-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00203-019-01658-4