Abstract
The effects of oxygen tensions on the antitumor activity of mitomycin-C (MMC) were surveyed using the human tumor clonogenic assay technique. Six human tumor xenografts (4 gastric cancers, and 2 colon cancers) were used in this study. Tumor cells were continuously exposed to MMC during the experimental period at various oxygen tensions, such as 2 per cent, which is considered to be hypoxic oxygen tension, 5 per cent which is considered as the physiological oxygen tension, and 20 per cent which is the conventionalin vitro culture condition. The antitumor activities of MMC on the 6 human tumor xenografts increased when the oxygen tension was lowered from 20 per cent to 5 per cent. However, no further increases of the antitumor activities of MMC were observed by lowering the oxygen tension from 5 to 2 per cent. Additionally, thein vitro antitumor activities of MMC at various oxygen tensions were compared with thein vivo chemosensitivities evaluated in nude mice. In five of the 6 human tumor xenografts,in vitro chemosensitivities assayed at 2 or 5 per cent oxygen tension were concordant within vivo chemosensitivities, althoughin vitro chemosensitivities assayed at 20 per cent were concordant within vivo chemosensitivities in 3 of the 6 tested tumors.
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References
Hamburger AW, Salmon SE. Primary bioassay of human stem cells. Science 1977; 197: 461–463.
Hirabayashi N, Yoshinaka K, Nosoh Y, Toge T, Niimoto M, Hattori T, Ohkita T.In vitro chemosensitivity tests on human tumor xenografts by clonogenic assay: combined use of Mitomycin C with-interferon or-interferon. Jpn J Surgery 1985; 15: 279–284.
Selby P, Buick RN, Tannock K. A critical appraisal of the “Human tumor stem cell assay”. New Eng J Med 1983, 308: 129–134.
Hirabayashi N, Nishiyama M, Yamaguchi M, Nosoh Y, Niimoto M, Hattori T. Effects of oxygen tension on tumor colony formations assayed by human tumor clonogenic assay. Jpn J Surgery 1986; 16: 148–151.
Teicher BA, Lazo JS, Sartorelli AC. Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells. Cancer Res 1981; 41: 73–81.
Kennedy AK, Rockwell S, Sartorelli AC. Preferential activation of Mitomycin C to cytotoxic metabolites by hypoxic tumor cells. Cancer Res 1980; 40: 73–81.
Kennedy AK, Teicher BA, Rockwell S, Sartorelli AC. The hypoxic tumor cell: a target for selective cancer chemotherapy. Biochem Pharmacol 1980; 29: 1–8.
Ovejera AA, Houchens DP, Baker AD. Chemotherapy of human tumor xenografts in genetically athymic mice. Annals of Clinical and Laboratory Science 1978; 8: 50–56.
Hanatani Y, Kubota T, Yamada Y, Tsuyuki K, Nakada M, Matsumoto S, Kumai K, Yoshino K, Ishibiki K, Abe O. Experimental chemotherapy of human carcinomas serially transplanted to nude mice. J Jpn Soc Cancer Ther 1980; 15: 1114–1120.
Ludwig CU, Peng YN, Beaudry JN, Salmon SE. Cytotoxity of Mitomycin C on clonogenic human carcinoma cells is not enhanced by hypoxia. Cancer Chemother Pharmacol 1984; 12: 146–150.
Nakada M. Chemosensitivity to Mitomycin C and cell kinetics of human tumor xenografts serially transplanted into nude mice. J Jpn Soc Surgery 1984; 85: 694–704.
Marshall RS, Rauth AM. Modification of the cytotoxic activity of Mitomycin C by oxygen and ascorbic acid in Chinese hamster ovary cells and repairdeficient mutant. Cancer Res 1986; 46: 2709–2713.
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Hirabayashi, N., Nishiyama, M., Niimi, K. et al. Effect of oxygen tension on the antitumor activity of mitomycin C assayed by human tumor clonogenic assay. The Japanese Journal of Surgery 17, 402–406 (1987). https://doi.org/10.1007/BF02470641
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DOI: https://doi.org/10.1007/BF02470641