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The prophylactic use of antibiotics in cell culture

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Abstract

This article describes the historical development of the prophylactic use of antibiotics in cell culture as well as their effects on cells. The influence of antibiotics on cell morphology, cellular degeneration and cell death and cellular function is summarized. Cellular DNA as well as protein synthesis are affected which can lead to interference with, or even changes in, metabolic processes. Such effects must be considered in cell culture research. As antibiotics are used in multifold ways, the otherwise standardized conditions in cell culture are no longer comparable. The prophylactic use of antibiotics is rejected for scientific reasons.

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References

  • Abraham EP, Chain E, Fletcher CM, Gardner AD, Heatley NG and Jennings MA (1941) Further observations on penicillin. The Lancet, 177–189.

  • Aubert-Tulkens G, van Hoof F and Tulkens P (1979) Gentamicin-induced lysosomal phospholipidosis in cultured rat fibroblasts. Laboratory Investigation 40, 481–491.

    Google Scholar 

  • Augusti-Tocco G and Sato G (1969) Establishment of functional clonal lines of neurons from mouse neuroblastoma. Proc. Natl. Acad. Sci. 64, 311–315.

    Google Scholar 

  • Baker LE and Ebeling AH (1939) Artificial maintenance media for cell and organ cultivation. I. The cultivation of fibroblasts in artificial and serumless media. J. Exp. Med. 69, 365.

    Google Scholar 

  • Banck G and Forsgren A (1979) Antibiotics and suppression of lymphocyte functionin vitro. Antimicrobial Agents and Chemotherapy 16, 554–560.

    Google Scholar 

  • Barnes D and Sato G (1980) Methods for growth of cultured cells in serum-free medium. Anal. Biochem. 102, 255–270.

    Google Scholar 

  • Barza M, Vine H and Weinstein L (1972) Reversibility of protein binding of penicillins: anin vitro study employing a rapid diafiltration process. Antimicrobial Agents and Chemotherapy 1, 427–432.

    Google Scholar 

  • Bettger WJ, Boyce ST, Walthall BJ and Ham RG (1981) Rapid clonal growth and serial passage of human diploid fibroblasts in a lipid-enriched synthetic medium supplement with epidermal growth factor, insulin and dexamethasone. Proc. Natl. Acad. Sci. 78, 5588–5592.

    Google Scholar 

  • Burrows MT (1910) The cultivation of tissues of the chick embryo outside the body. Am. Med. Ass. 55, 2057–2058.

    Google Scholar 

  • Cahn RD and Cahn MB (1966) Heritability of cellular differentiation: clonal growth and expression of differentiation in retinal pigment cellsin vitro. Proc. Natl. Acad. Sci. 55, 106–114.

    Google Scholar 

  • Carrell A (1912) On the permanent life of tissue outside of the organism. J. Exp. Med. 15, 516–528.

    Google Scholar 

  • Carrel A (1913) Artificial activation of the growthin vitro of connective tissue. J. Exp. Med. 17, 14–19.

    Google Scholar 

  • Carrel A (1924) Tissue Culture and Cell Physiologie. Physiological Reviews 4, 1–20.

    Google Scholar 

  • Carrel A, and Ebeling AH (1922) Pure cultures of large mononuclear leucocytes. J. Exp. Med. 36, 365–377.

    Google Scholar 

  • Casemore DP (1967) Gentamicin as a bactericidal agent in virological tissue cultures. J. Clin. Path. 20, 298–299.

    Google Scholar 

  • Choi KW and Bloom AD (1970) Cloning human lymphocytesin vitro. Nature 227, 171–173.

    Google Scholar 

  • Chow BF and McKee CM (1945) Interaction between cristalline penicillin and human plasma proteins. Science 101, 67–68.

    Google Scholar 

  • Chung SD, Alavi N, Livingstone D, Hiller S and Taub M (1982) Characterization of primary rabbit kidney cultures that express proximal tubule functions in a hormonal defined medium. Cell Biol. 95, 118–126.

    Google Scholar 

  • Collins JF (1965) Antibiotics, proteins and nucleic acids. Brit. Med. Bull. 21, 223–228.

    Google Scholar 

  • Coon HG (1966) Clonal stability and phenotypic expression of chick cartilage cellsin vitro. Proc. Natl. Acad. Sci. 55, 66–73.

    Google Scholar 

  • Cottagnoud P and Neftel KA (1986) Beta-lactams act on DNA synthesis in K-562 cells. Cell Biology and Toxicology 2, 523–72.

    Google Scholar 

  • Cruickshank CND and Lowbury EJL (1952) Effect of antibiotics on tissue cultures of human skin. British Medical Journal, 1070–1072.

  • Dickman KG and Mandel LJ (1989) Glycolytic and oxidative metabolism in primary renal proximal tubule cultures. Am. J. Physiol. 257, 333–340.

    Google Scholar 

  • Dickman KG and Renfro JL (1990) Streptomycin toxicity in primary cultures of flounder renal proximal tubule cells. In Vitro 26, 571–578.

    Google Scholar 

  • Doljanski L, Hoffman RS and Tenenbaum E (1944) The effect of tumor extracts on growth of cellsin vitro. Growth 8, 13.

    Google Scholar 

  • Doljanski L and Werner H (1945) Studies on groth-promoting factors of adult tissue extracts; precipitation with alcohol; action of lipid solvents. Growth 9, 229.

    Google Scholar 

  • Drew AH (1927) The action of tumor extracts on tissuesin vitro. Brit. J. Exp. Path. 8, 176.

    Google Scholar 

  • Eagle H (1954) The binding of penicillin in relation to its cytotoxic action. III: The binding of penicillin by mammalian cells in tissue culture (HeLa and L strains). J. Exp. Mod. 100, 117–124.

    Google Scholar 

  • Eagle H (1955) Nutrition needs of mammalian cells in tissue culture. Science 122, 501.

    Google Scholar 

  • Eagle H (1959) Amino acid metabolism in mammalian cell cultures. Science 130, 432.

    Google Scholar 

  • Eagle H, Agranoff BW and Snell EE (1960) The biosynthesis of meso-inositol by cultured mammalian cells and the parabiotic growth of inositol-dependent and inositol-independent strains. J. Biol. Chem. 235, 1891.

    Google Scholar 

  • Earle WR (1934) A technique for the adjustment of oxygen and carbon dioxide tensions and hydrogen ion concentration, in tissue cultures planted in Carrel flasks. Arch. exp. Z. 16, 116.

    Google Scholar 

  • Ebeling AH (1919) A strain of connective tissue seven years old. J. Exp. Med. 30, 531–537.

    Google Scholar 

  • Ebeling AH (1922) A ten year old strain of fibroblasts. J. Exp. Med. 25, 755–757.

    Google Scholar 

  • Fischer A (1939) Nature of the growth-accelerating substance of animal tissue cells. Nature (Lond.) 144, 113.

    Google Scholar 

  • Fischer A (1941) The nature of the growth-promoting substances in embryonic tissue juice. Acta Phys. Scand. 3, 54.

    Google Scholar 

  • Fischer A (1941) Die Bedeutung der Aminosäuren für die Gewebezellenin vitro. Acta Phys. Scand. 2, 143–188.

    Google Scholar 

  • Fischer A, Astrup T, Ehrenswärd G and Oehlenschläger V (1948) Growth of animal tissue cells in artificial medium. Proc. Soc. Exp. Biol. 67, 40.

    Google Scholar 

  • Fram RJ (1986) A comparison of the effects of cytosine arabinoside and beta-lactams on DNA synthesis and cellular proliferation. Cell Biology and Toxicology 2, 531–539.

    Google Scholar 

  • Ghosh P and Chatterjee S (1987) Effects of gentamicin on sphingomyelinase activity in cultured human renal proximal tabular cells. J. Biol. Chem. 262, 12550–12556.

    Google Scholar 

  • Gilbert DN, Kutscher E, Ireland P, Barnett JA and Sanford JP (1971) Effect of the concentrations of magnesium and calcium on thein vitro-susceptibility ofPseudomonas aeruginosato gentamicin. J. Infec. Dis. 124, 37–45.

    Google Scholar 

  • Gordon RC, Regamey C and Kirby WMM (1972) Serum protein binding of the aminoglycoside antibiotics. Antimicrobial Agents and Chemotherapy 2, 214–216.

    Google Scholar 

  • Hammond SL, Ham RG and Stampfer MR (1984) Serum-free growth of human mammary epithelial cells: rapid clonal growth in defined medium and extended serial passage with pituitary extract. Proc. Natl. Acad. Sci. 81, 5435–5439.

    Google Scholar 

  • Harrison RG (1907) Observation on the living developing nerve fiber. Proc. Soc. Exp. Biol. Med. 4, 140–143.

    Google Scholar 

  • Hartmann G, Behr W, Beissner K-A, Honikel K and Sippel A (1968) Antibiotica als Hemmstoffe der Nucleinsäure- und Proteinsynthese. Angewandte Chemie 18, 710–718.

    Google Scholar 

  • Hayashi J and Sato GH (1976) Replacement of serum by hormones permits growth of cells in a defined medium. Nature 259, 132–134.

    Google Scholar 

  • Heilmann E (1945) Cytotoxicity of Streptomycin and Streptothricin. Proc. Soc. Exp. Biol. 60, 365–367.

    Google Scholar 

  • Hemphill JJ, Herman YF and Young VM (1957) Comparative antifungal activity of nystatin and amphotericin B in tissue culture for virus propagation. Antibiotics Ann. 961–966.

  • Hetherington DC and Craig JS (1939) Effect of frozen-dried plasma and frozen-dried embryo juice on tissue cultures. Proc. Soc. Exp. Biol. (N.Y.) 42, 831.

    Google Scholar 

  • Hoffman RS and Doljanski L (1939) The growth activating effect of extracts of adult tissue on fibroblasts coloniesin vitro. Experiments with chicken heart extracts. Growth 3, 61.

    Google Scholar 

  • Hori R, Yamamoto K, Saito H, Kohno M and Inui K-I (1984) Effects of aminoglycoside antibiotics on cellular function of kidney epithelial cell line (LLC-PK1): A model system for aminoglycoside nephrotoxicity. The Journal of Pharmacology and Experimental Therapeutics 230, 742–748.

    Google Scholar 

  • Hoshi H, Kan M, Chen J-K and McKeehan WL (1988) Comparative endocrinology-autocrinology of human adult large vessel endothelial and smooth muscle cells. In vitro Cell. Dev. Biol. 24, 309–320.

    Google Scholar 

  • Huebscher U, Huynh UD, Hässig M and Neftel KA (1986) Effects of beta-lactams on DNA replication. Cell Biology and Toxicology 2, 541–548.

    Google Scholar 

  • Huegin AW, Cerny A, Zinkernagel RM and Neftel KA (1986) Suppressive effects of β-lactam-antibiotics onin vitro generation of cytotoxict-cells. Int. J. Immunopharmac. 8, 723–729.

    Google Scholar 

  • Huynh UD, Neftel KA, Spadari S and Hübscher U (1987) Betalactam antibiotics interfere with eukaryotic DNA-replication by inhibiting DNA polymerase A. Nucleic Acids Research 15, 10496–10506.

    Google Scholar 

  • Ikegaki K (1950) Effects of streptomycin on the growth of normal tissue cellsin vitro. Journal of Antibiotics 4, 311–313.

    Google Scholar 

  • Jacoby F (1936) Migratory and mitotic activity of chick fibroblasts under the influence of dialysate of embryo juice. Arch. exp. Z. 19, 241.

    Google Scholar 

  • Kano-Sueoka T, Cohen DM, Yamaizumi Z, Nishimura S, Mori M and Fujiki H (1979) Phosphoethanolamine as a growth factor of the mammary carcinoma cell line of rat. Proc. Natl. Acad. Sci. 76, 5741–5744.

    Google Scholar 

  • Keilova H (1948) The effect of streptomycin on tissue cultures. Experientia 4, 483–484.

    Google Scholar 

  • Keen PM (1966) The binding of penicillins to bovine serum albumin. Biochemical Pharmacology 15, 447–463.

    Google Scholar 

  • Krebs HA (1950) Body size and tissue respiration. Biochimica and Biophysica Acta 4, 249–269.

    Google Scholar 

  • Kuhlmann I, Kurth W and Ruhdel I (1989)In vivo-undin vitro-Produktion monoklonaler Antikörper im Labormaßstabe. Forum Mikrobiologie 12, 451–457.

    Google Scholar 

  • Kuhlmann I, Kurth W and Ruhdel I (1989) Monoclonal antibodies:in vivo- andin vitro-production on a laboratory scale with consideration of the legal aspects of animal protection. ATLA 17, 72–82.

    Google Scholar 

  • Lange A and Assmann G (1966) Penetration von Penicillin G und Ampicillin in Mäusefibroblasten (Earle's strain L). Z. med. Mikrobio. u. Immunol. 153, 60–67.

    Google Scholar 

  • Laska DA, Williams PD, White SL, Thompson CA and Hoover DM (1990)In vitro correlation of ultrastructural morphology and creatine phosphokinase relase in L6 skeletal muscle cells after exposure to parenteral antibiotics. In vitro Cell. Dev. Biol. 26, 393–398.

    Google Scholar 

  • Litwin J (1970) The effect of commercial and pure gentamicin on the growth of human diploid lung fibroblasts. Acta path. microbiol. scand. Section B. 78, 273–276.

    Google Scholar 

  • Lindl T and Bauer J (1989) Zell- und Gewebekultur. 2. Aufl., Gustav Fischer Verlag, Stuttgart/New York.

    Google Scholar 

  • Lynch RM and Balaban RS (1987) Energy metabolism of renal cell lines, A6 and MDCK: regulation by Na−K-ATPase., Am. J. Physiol. C225–C231.

  • McKeehan WL and Adams PS (1986) Assay of growth factors for prostate epithelial cells. Journal of tissue culture methods 10, 151–154.

    Google Scholar 

  • McKeehan WL, Adams PS and Fast D (1987) Different hormonal requirements for androgen-independent growth of normal and tumor epithelial cells from rat prostate. In Vitro Cell. Dev. Biol. 23, 147–152.

    Google Scholar 

  • McKeehan WL, Adams PS and Rossner MP (1984) Direct mitogenic effects of insulin, epidermal growth factor, glucocorticoid, cholera toxin, unknown pituitary factors and possibly prolactin, but not androgen, on normal rat prostate epithelial cells in serum-free, primary cell culture. Cancer Research 44, 1998–2010.

    Google Scholar 

  • McKeehan WL, Barnes D, Reid L, Stanbridge E, Murakami H and Sato GH (1990) Frontiers in mammalian cell culture. In Vitro Cell. Dev. Biol. 26, 9–23.

    Google Scholar 

  • McKeehan WL, Hamilton WG and Ham RG (1976) Selenium is an essential trace nutrient for growth of WI-38 diploid human fibroblasts. Proc. Natl. Acad. Sci. 73, 2023–2027.

    Google Scholar 

  • McLimans WF, Bonissol C, Davis EV, Glover FI and Rake G (1955/1956) Nystatin, an antibiotic useful for the control of fungal and yeast contaminants in tissue culture. Antibiotics Annual. 691–696.

  • McLimans WF, Davis EV, Glover FI and Rake GW (1957) The submerged culture of mammalian cells: the spinner culture. J. Immunol. 79, 428–433.

    Google Scholar 

  • Medawar PB (1940) The growth, growth energy, and ageing of the chicken's heart. Proc. Roy. Soc. B. 129, 332–355.

    Google Scholar 

  • Misfeldt DS and Sanders MJ (1981) Transepithelial transport in cell culture: D-glucose transport by a pig kidney cell line (LLC-PK1). J. Membrane Biol. 59, 13–18.

    Google Scholar 

  • Morgan JF, Morton HJ and Parker RC (1950) Nutrition of animal cells in tissue culture. I. Initial studies on a synthetic medium. Proc. Soc. Exp. Biol. Med. 73, 1–8.

    Google Scholar 

  • Moskowitz M and Kelker NE (1963) Sensitivity of cultured mammalian cells to streptomycin and dihydrostreptomycin. Science 141, 647–648.

    Google Scholar 

  • Moss PS, Spector DH, Glass CA and Strohman RC (1984) Streptomycin retards the phenotypic maturation of chick myogenic cells. In Vitro 20, 473–478.

    Google Scholar 

  • Neftel KA, Hauser SP and Müller MR (1985) Inhibition of granulopoiesisin vivo andin vitro by β-lactam antibiotics. J. Infect. Dis. 152, 90–98.

    Google Scholar 

  • Neftel KA and Hübscher U (1987) Effects of β-lactam antibiotics on proliferating eukaryotic cells. Antimicrobial agents and chemotherapy 31, 1657–1661.

    Google Scholar 

  • Neftel KA, Huynh UD and Hübscher U (1989) Effect of beta-lactam antibiotics on eukaryotic DNA replication: possible impact on the host-parasite relationship. In: Gillisen, G., Opferkuch, W., Peters, G., Pulverer, G. (eds.) The influence of antibiotics on the host-parasite relationship III. Springer Berlin, Heidelberg.

    Google Scholar 

  • Neftel KA, Müller MR, Wälti M, Erni J, Gugler M and Arrenbrecht S (1983) Penicilin-G degradation products inhibitin vitro granulopoiesis. British Journal of Haematology 54, 255–260.

    Google Scholar 

  • Neftel KA, Müller MR, Widmer U and Hügin AW (1986) Beta-lactam antibiotics inhibit humanin vitro granulopiesis and proliferation of some other cell types. Cell Biology and Toxicology 2, 513–521.

    Google Scholar 

  • Owens O, Gey MK and Gey GO (1954) Growth of cells in agitated fluid medium. Annals New York Academy of Sciences 58, 1039–1055.

    Google Scholar 

  • Paul MO and Beswick TSL (1982) The fate of antibiotics added to cell cultures used in virology. Journal of Virological Methods 4, 55–61.

    Google Scholar 

  • Perlman D, Giuffre NA and Brindle SA (1961) Use of fungizoner in control of fungi and yeasts in tissue culture. Proc. Soc. Exp. Biol. Med. 106, 880–883.

    Google Scholar 

  • Perlman D, Giuffre NA, Jackson PW and Giardinello FE (1959) Effects of antibiotics on multiplication of L cells in suspension culture. Proc. Soc. Exp. Biol. Med. 102, 290–292.

    Google Scholar 

  • Perlman D (1979) Use of Antibiotics in Cell Culture Media. Methods Enzymol. 58, 110–116.

    Google Scholar 

  • Puck TT, Marcus PI and Cieciura SJ (1956) Clonal growth of mammalian cellsin vitro. J. Exp. Med. 103, 273–283.

    Google Scholar 

  • Ramirez-Ronda CH, Holmes RK and Sanford JP (1975) Effects of divalent cations on binding of aminoglycoside antibiotics to human serum proteins and to bacteria. Antimicrobial Agents and Chemotherapy 7, 239–245.

    Google Scholar 

  • Ramsammy LS, Josepovitz C, Lane B and Kaloyanides GJ (1989) Effects of gentamicin on phospholipid metabolism in cultured rabbit proximal tubular cells. Am. J. Physiol. 256, 204–213.

    Google Scholar 

  • Rolinson GN and Sutherland R (1965) The binding of antibiotics to serum proteins. Brit. J. Pharmacol. 25, 638–650.

    Google Scholar 

  • Ruhdel IW (1992) Herstellung undin vitro-Produktion monoklonaler Antikörper gegen die schweren Ketten des Myosins, eine Alternativmethode zum Tierversuch. Unveröff. Dissertation, Universität Konstanz.

  • Sato G, Zaroff L and Mills SE (1956) Tissue culture populations and their relation to the tissue of origin. Proc. N. A. S. 46, 963–972.

    Google Scholar 

  • Schafer TW, Pascale A, Shimonaski G and Came PE (1972) Evaluation of gentamicin for use in virology and tissue culture. Applied Microbiology 23, 565–570.

    Google Scholar 

  • Schindler R, Day M and Fischer GA (1959) Culture of neoplastic mast cells and their synthesis of 5-hydroxytryptamine and histaminein vitro. Cancer Res. 19, 47–51.

    Google Scholar 

  • Schwartze PE and Seglen PO (1981) Effects of antibiotics on protein synthesis and degradation in primary cultures of rat hepatocytes. In Vitro 17, 71–76.

    Google Scholar 

  • Schwertz DW, Kreisberg JI and Venkatachalam MA (1986) Gentamicin-induced alterations in pig kidney epithelial (LLC-PK1) cells in culture. The Journal of Pharmacology and Experimental Therapeutics 236, 254–262.

    Google Scholar 

  • Sens MA, Hennigar GR, Hazen-Martin DJ, Blackburn JG and Sens DA (1988) Cultured human proximal tubule cells as a model for aminoglycoside nephrotoxicity. Annals of clinical and laboratory science 18, 204–214.

    Google Scholar 

  • Siminons CF, Bogusky RT and Humes HD (1980) Inhibitory effects of gentamicin on renal mitochondrial oxidative phosphorylation. The Journal of Pharmacology and Experimental Therapeutics 214, 709–715.

    Google Scholar 

  • Smith CG, Lummis WL and Grady JE (1959) An improved tissue culture assay. II. Cytotoxicity studies with antibiotics, chemicals, and solvents. Cancer Research 19, 847–852.

    Google Scholar 

  • Thompson EB, Tomkins GM and Curran JF (1966) Induction of tyrosine α-ketoglutarate transaminase by steroid hormones in a newly established tissue culture cell line. Proc. Natl. Acad. Sci. 56, 236–303.

    Google Scholar 

  • Tompsett R, Shultz S and McDermott W (1947) The relation of protein binding to the pharmacology and antibacterial activity of penicillins X, G, dihydro-F and K. J. Bact. 53, 581–595.

    Google Scholar 

  • Tsao MC, Walthall BJ and Ham RG (1982) Clonal growth of normal human epidermal keratinocytes in a defined medium. Journal of cellular physiology 10, 219–229.

    Google Scholar 

  • Tulkens P and Trouet A (1974) Uptake and intracellular localization of kanamycin and gentamycin in the lysosomes of cultured fibroblasts. Arch. Int. de Physiol. et de Biochimie 82, 1018–1019.

    Google Scholar 

  • Viano I, Eandi M and Santiano M (1983) Toxic effects of some antibiotics on rabbit kidney cells. Int. J. Tiss. Reac. 5, 181–186.

    Google Scholar 

  • Vogelaar JPM and Erlichman E (1933) A feeding solution for cultures of human fibroblasts. Amer. J. Cancer 18, 28–38.

    Google Scholar 

  • Vonen B and Morland J (1982) Penicillin toxicity in isolated rat hepatocytes revealed by decreased incorporation of valine into proteins. Acta pharmacol. et toxicol. 51, 81–86.

    Google Scholar 

  • White PR (1946) Cultivation of animal tissuesin vitro in nutrients of precisely known constitution. Growth 10, 231–289.

    Google Scholar 

  • White PR (1949) Prolonged survival of excised animalin vitro in nutrients of known constitution. Growth 10, 231.

    Google Scholar 

  • Yaffe D (1968) Retention of differentiation potentialities during prolonged cultivation of myogenic cells. Proc. N. A. S. 61, 477–483.

    Google Scholar 

  • Yasumura Y, Tashjian AH and Sato GH (1966) Establishment of four functional, clonal strains of animal cells in culture. Science 154, 1186–1189.

    Google Scholar 

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  1. Tierforschungsanlage, Universität Konstanz, 78343, Konstanz, Germany

    Ingrid Kuhlmann

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Kuhlmann, I. The prophylactic use of antibiotics in cell culture. Cytotechnology 19, 95–105 (1995). https://doi.org/10.1007/BF00749764

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