Porfiromycin as a Bioreductive Alkylating Agent with Selective Toxicity to Hypoxic EMT6 Tumor Cells in Vivo and in Vitro

Cancer Research

Volumn 45, Issue 8, 1985, Pages 3642-3645

  Keyes, Susan R ^a   Sartorelli, Alan C ^a   Rockwell, Sara ^a  

^a YALE CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MITOMYCIN C; PORFIROMYCIN;

ANIMAL MODEL; CHEMOTHERAPY; CYTOTOXICITY; DRUG MIXTURE; HYPOXIC CELL; IN VITRO STUDY; INTRAPERITONEAL DRUG ADMINISTRATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; RADIOTHERAPY; THERAPY;

ALKYLATING AGENTS; ANIMAL; CELL SURVIVAL; CELLS, CULTURED; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; MAMMARY NEOPLASMS, EXPERIMENTAL; MICE; MICE, INBRED BALB C; MITOMYCIN; MITOMYCINS; OXYGEN; PORFIROMYCIN; SUPPORT, NON-U.S. GOV'T;

EID: 0021971997     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: None     Document Type: Article

References (22)

1. Kennedy. K. A., Teicher, B. A., Rockwell, S., and Sartorelli, A. C. The hypoxic tumor cell: a target for selective cancer chemotherapy. Biochem. Pharmacol., 29:1–8.1980.
2. Moulder, J. E., and Rockwel.S. Hypoxic fractions of sold tumors: experimental techniques, methods of analysis, and a survey of existing data. Int. J. Racial Oncol. Biol. Phys., 10: 695–712,1984.
3. Kennedy, K. A., Rockwell, S., and Sartorelli, A. C. Preferential activation of mitomycin C to cytotoxic metabolites by hypoxic tumor cels. Cancer Res., 40: 2356–2360,1980.
4. Keyes. S. R. Fracasso, P. M., Heimbrook, D. C., Rockwell, S., Sligar, S. G., and Sartorelli, A. C. Role of NADPH-cytochrome c reductase and DT-diaphorase in the biotransformation of mitomycin C. Cancer Res., 44: 5638–5643, 1984.
5. Keyes, S. R., Rockwell, S. and Sartorelli, A. C. Enhancement of mitomycin C cytotoxicity to hypoxic tumor cells by dicoumarol in vitro and in vivo. Cancer Res., 45:213–216,1985.
6. Rockwel, S., Kennedy. K. A., and Sartorelli, A. C. Mitomycin C as a prototype bioreductive alkylating agent in vitro studies of metabolism and cytotoxicity. Int. J. Racial Oncol. Biol. Phys., 8:753–755,1982.
7. Rockwell, S. Effects of mitomycin C alone and in combination with X-rays on EMT6 mouse mammary tumors in vivo. J. Natl. Cancer Inst., 71: 765–771, 1983.
8. Rockwell, S., and Kennedy. K. A. Combination therapy with radiation and mitomycin C: preliminary results with EMT6 tumor cells in vitro and in vivo. Int. J. Racial Oncol. Biol. Phys., 5; 1673–1676,1979.
9. Keyes, S. R., Heimbrook, D. C., Fracasso. P. M., Rockwel, S., Sligar, S. G., and Sartorelli, A. C. Chemotherapeutic attack of hypoxic tumor cells by the bioreductive alkylating agent mitomycin C. Adv. Enzyme Regul., in press, 1985.
10. Wheeler, B. P., Bowdon, B. J., Gremsley, J. A., and Lloyd, H. H. Interrelationships of some chemical, physiochemical, and biological activities of several 1Haloethyl)-1 -nitrosoureas. Cancer Res., 34:194–200,1974.
11. Rockwel, S. In vivo-in vitro tumor systems: new models for studying the response of tumors to therapy. Lab. Anim. Sci., 27:831 -851,1977.
12. Rockwel, S., and Schulz, R. J. Failure of 5-thio-D-glucose to alter cell survival in irradiated and unirradiated EMT6 tumors. Radial Res., 100:527–535,1984.
13. Rockwel, S. Effect of host age on the transplantation, growth, and radiation response of EMT6 tumors. Cancer Res., 41:527–531.1981.
14. Rockwel, S., and Kallman, R. F. Cellular radiosensitivity and tumor radiation response in the EMT6 tumor eel system. Radial Res., 53:281–294,1973.
15. Rockwel, S. Cytotoxicities of mitomycin C and X-rays to aerobic and hypoxic cells in vitro, bit J. Racial Oncol. Biol. Phys. 8:1035–1039,1982.
16. Iyer, V. N., and Szybalski, W. Mitomycins and porfiromycin: chemical mechanisms of activation and cross-Inking of DNA. Science (Wash. DC), 145: 55–58,1964.
17. Lisio, A. U. and Weissbach, A. The localization of [14c]porfiromycin in Escherichia coii and γ-phage. Biochim. Biophys. Acta, 107:215–221,1965.
18. Tomasz, M., Mercado, C. M., Olson, J., and Chatterjie, N. The mode of interaction of mitomycin C with deoxyribonucleic acid and other polynudeotides in vitro. Biochemistry, 73:4878–4887.1974.
19. Weaver, J., and Tomasz, M. Reactivity of mitomycin C with synthetic polyribonucleotides containing guanine or guanine analog. Biochim. Biophys. Acta, 697:252–254.1982.
20. Weissbach. A., and Lisio, A. Alkylation of nucleic acids by neomycin C and porfiromycin. Biochemistry, 4:196–200,1965.
21. Steel, G. G., and Peckham, M. J. Exploitable mechanisms in combined radio-therapy-chemotherapy: the concept of addrtivity. Inl J. Radial Oncol. Biol. Phys., 5:85–91,1979.
22. Kinoshita, S. Uzu. K. Nakano, K., Shimizu, M., Takahashi, T., and Matsui, M. Mitomycin derivatives. I. Preparation of mitosane and mitosene compounds and their biological activities. J. Med. Chem. 14:103–109,1971.