Summary
The fraction of clonogenic cells (as assayed by colony formation in semisolid agar medium) in neurogenic TV1A tumor transplants carried subcutaneously by hyperglycemic BDIX rats (serum glucose concentration 50 mmoles/l; average intratumoral pH 6.1) was reduced by a factor of approximately 2.5x103 after in vivo exposure to 42.2°C for 1 h. The corresponding reduction factor for TV1A tumors in normoglycemic rats was about 20 (serum glucose concentration 6 mmoles/l; average intratumoral pH 6.9). Hyperglycemia without hyperthermic treatment reduced clonogenicity by a factor of about 18 (“glucose-mediated suicide”).
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Baba T, Kidera Y, Kimura NT, Aoki K, Kamura T, Taniguchi S, Nishikawa K (1978) 5-Fluorouracil-0-β-d-glucuronide as a newly synthesized chemically modified, nontoxic anticancer drug. Gann 69:283–284
Bicker U (1974) Application of β-d-glucuronides and glucose together suggests a new direction for cancer chemotherapy. Nature 252:726–727
Calderwood SK, Dickson JA (1980) Effect of hyperglycemia on blood flow, pH, and response to hyperthermia (42°C) of the Yoshida sarcoma in the rat. Cancer Res 40:4728–4733
Dahl O (1980) Effects of hyperthermia on a neurogenic rat cell line (BT4C) in culture. Development of thermal tolerance during continuous heating. Acta Radiol Oncol 19:489–496
Dickson JA, Calderwood SK (1979) Effects of hyperglycemia and hyperthermia on the pH, glycolysis, and respiration of the Yoshida sarcoma in vivo. J Natl Cancer Inst 63:1371–1381
Druckrey H (1971) Genotypes and phenotypes of ten inbred strains of BD-rats. Arzneim Forsch 21:1274–1278
Freeman ML, Raaphorst GP, Hopwood LE, Dewey WC (1980) The effect of pH on cell lethality induced by hyperthermic treatment. Cancer 45:2291–2300
Gerweck LE (1977) Modification of cell lethality at elevated temperatures. Radiat Res 70:224–235
Gullino PM, Clark SH, Grantham FH (1964) The interstitial fluid of solid tumors. Cancer Res 24:780–794
Jähde E, Rajewsky MF (1981 a) Tumor-selective modification of cellular microenvironment in vivo. I. Effect of hyperglycemia on H+-ion concentration in normal and malignant tissues. J Cancer Res Clin Oncol 99:A12
Jähde E, Rajewsky MF (1981 b) Tumor-selective modification of cellular microenvironment in vivo. II. Effect of hyperglycemia on the thermal sensitivity of clonogenic tumor cells. J Cancer Res Clin Oncol 99:A53
Jähde E, Rajewsky MF (1982) Tumor-selective modification of cellular microenvironment in vivo: Effect of glucose infusion on the pH in normal and malignant rat tissues. Cancer Res 42:1505–1512
Jähde E, Rajewsky MF, Baumgärtl H (1982) pH distributions in transplanted neural tumors and normal tissues of BDIX-rats as measured with pH microelectrodes. Cancer Res 42:1498–1504
Kahler H, Robertson WV (1943) Hydrogen-ion concentration of normal liver and hepatic tumors. J Natl Cancer Inst 3:495–501
Laerum OD, Rajewsky MF (1975) Neoplastic transformation of fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. J Natl Cancer Inst 55:1177–1187
Laerum OD, Rajewsky MF, Schachner M, Stavrou D, Haglid KG, Haugen Å (1977) Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. Z Krebsforsch 89:273–295
Lippmann HG, Graichen D (1977) Glukose- und K+-Bilanz während hochdosierter intravenöser Glukosezufuhr. Infusionstherapie 4:166–178
Nielsen OS, Overgaard J (1979) Effect of extracellular pH on thermotolerance and recovery of hyperthermic damage in vitro. Cancer Res 39:2772–2778
Rauen HM, Friedrich M, Norpoth K (1968) Messungen zur Manipulation der Glukose-abhängigen Tumorsäuerung in vivo. Z Naturforsch 23b:1461–1475
Saito Y, Baumgärtl H, Lübbers DW (1976) The RF sputtering technique as a method for manufacturing needle-shaped pH microelectrodes. In: Kessler M, Clark LC, Lübbers DW, Silver IA, Simon W (eds) Ion and enzyme electrodes in biology and medicine. Urban & Schwarzenberg, Munich, pp 103–109
Steiger E, Vars HM, Dudrick J (1972) A technique for long-term intravenous feeding in unrestrained rats. Arch Surg 104:330–332
Stevens CD, Mosteller RC (1969) Enhancement by glucose of the inhibition of an Ehrlich ascites tumor by tetraazatricyclododecance. Cancer Res 29:1132–1136
Vaupel PW, Frinak S, Bicher HI (1981) Heterogenous oxygen partial pressure and pH distribution in C3H mouse mammary adenocarcinoma. Cancer Res 41:2008–2013
Vaupel P, Günther H, Grote J, Aumüller G (1971) Atemgaswechsel und Glukosestoffwechsel von Tumoren (DS-Carcinosarkom) in vivo. I. Experimentelle Untersuchungen der versorgungsbestimmenden Parameter. Z Ges Exp Med 156:283–294
Von Ardenne M, Reitnauer PG (1980) Selective Inhibition of microcirculation in tumor tissue. Naturwissenschaften 67:154
Von Ardenne M, Reitnauer PG, Rohde K, Westmeyer H (1969) in vivo-pH-Messungen in Krebs-Mikrometastasen bei optimierter Übersäuerung. Z Naturforsch 24b:1610–1619
Warburg O (ed) (1926) Über den Stoffwechsel der Tumoren. Springer, Berlin
Yatvin MB, Kreutz W, Horwitz BA, Shinitzky M (1980) pH-sensitive liposomes: Possible clinical implications. Science 210:1253–1255
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Jähde, E., Rajewsky, M.F. Sensitization of clonogenic malignant cells to hyperthermia by glucose-mediated, tumor-selective pH reduction. J Cancer Res Clin Oncol 104, 23–30 (1982). https://doi.org/10.1007/BF00402050
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DOI: https://doi.org/10.1007/BF00402050