Modification of the Metabolism and Cytotoxicity of Bioreductive Alkylating Agents by Dicoumarol in Aerobic and Hypoxic Murine Tumor Cells

Cancer Research

Volumn 49, Issue 12, 1989, Pages 3310-3313

  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

3 METHYLCHOLANTHRENE; ALKYLATING AGENT; DICOUMAROL; DOXORUBICIN; MITOMYCIN; N(6) ((DIMETHYLAMINO)METHYLENE)MITOMYCIN C; N(6)-((DIMETHYLAMINO)METHYLENE)MITOMYCIN C; PORFIROMYCIN; VITAMIN K GROUP; 7 N (DIMETHYLAMINOMETHYLENE)MITOMYCIN C; MITOMYCIN C; RADIOISOTOPE;

AEROBIC METABOLISM; ANAEROBIC GROWTH; ANIMAL; ARTICLE; CELL LINE; CELL SURVIVAL; DRUG EFFECT; EXPERIMENTAL NEOPLASM; KINETICS; METABOLISM; MOUSE; OXIDATION REDUCTION REACTION; TRANSPORT AT THE CELLULAR LEVEL; ANIMAL CELL; CELL CULTURE; DRUG CYTOTOXICITY; HYPOXIA; NONHUMAN; PRIORITY JOURNAL; TUMOR CELL;

AEROBIOSIS; ALKYLATING AGENTS; ANAEROBIOSIS; ANIMAL; BIOLOGICAL TRANSPORT; CELL LINE; CELL SURVIVAL; DICUMAROL; DOXORUBICIN; KINETICS; MAMMARY NEOPLASMS, EXPERIMENTAL; METHYLCHOLANTHRENE; MICE; MITOMYCINS; OXIDATION-REDUCTION; PORFIROMYCIN; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, P.H.S.; VITAMIN K;

EID: 0024475230     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: None     Document Type: Article

References (29)

1. Kennedy, K. A., Rockwell, S., and Sartorelli, A. C. Preferential activation of mitomycin C to cytotoxic metabolites by hypoxic tumor cells. Cancer Res., 40:2356–2360,1980.
2. Kennedy, K. A., Sligar, S. G., Polomski, L., and Sartorelli, A. C. Metabolic activation of mitomycin C by liver microsomes and nuclei. Biochem. Pharmacol., 31:2011–2016,1982.
3. 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.
4. Komiyama, T., Old, T., and Inui, T. Activation of mitomycin C and quinone drug metabolism by NADPH-cytochrome P-450 reductase. J. Pharm. Dyn., 2:407–410,1979.
5. Pan, S-S., Andrews, P. A., Glover, C. J., and Bachur, N. R. Reductive activation of mitomycin C and mitomycin C metabolites catalyzed by NADPH-cytochrome P-450 reductase and xanthine oxidase. J. Biol. Chem., 259:959–966,1984.
6. Pritsos, C. A., Pardini, L. L., Elliot, A. J., and Pardini, R. S. Relationship between the antioxidant enzyme DT-diaphorase and tumor response to mitomycin C treatment. In: M. G. Simic and K. A. Taylor (eds.), Oxygen Radicals in Biology and Medicine, pp. 1–4. New York: Plenum Publishing Corp., 1987.
7. Ernster, L. DT-diaphorase. Methods Enzymol., 10: 309–317, 1967.
8. Keyes, S. R., Rockwell, S., and Sartorelli, A. C. Enhancement of mitomycin C cytotoxicity to hypoxic tumor cells by dicoumarol in vivo and in vitro. Cancer Res., 45:213–216,1985.
9. Rockwell, S., Keyes, S. R., and Sartorelli, A. C. Modulation of the cytotoxicity of mitomycin C by dicoumarol in vitro. Cancer Res., 48: 5471–5474, 1988.
10. Lind, G., Vadi, H., and Ernster, L. Metabolism of benzo(a]pyrene-3,6-quinone and 3-hydroxybenzo(a]pyrene in liver microsomes from 3-methylcholanthrene-treated rats. Arch. Biochem. Biophys., 190:97–108,1978.
11. Benson, A. M., Hunkeler, M. J., and Talalay, P. Increase of NAD(P)H:quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity. Proc. Natl. Acad. Sci. USA, 77: 5216–5220,1980.
12. Thor, H., Smith, M. T., Hartzeil, P., Bellomo, G., Jewell, S. A., and Orrenius, S. The metabolism of menadione (2-methyl-l,4-naphthoquinone) by isolated hepatocytes: a study of the implication of oxidative stress in intact cells. J. Biol. Chem., 257:12419–12425,1982.
13. Keyes, S. R., Rockwell, S., and Sartorelli, A. C. Correlation between drug uptake and selective toxicity of porfiromycin to hypoxic EMT6 cells. Cancer Res., 47:5654–5657,1987.
14. Iyer, V. N., and Szybalski, W. Mitomycin and porfiromycin: chemical mechanisms of activation and cross-linking of DNA. Science (Wash. DC), 145: 55–58,1964.
15. Kennedy, K. A., McGurl, J. D., Leondaridis, L., and Alabaster, O. pH dependence of mitomycin C-induced cross-linking activity in EMT6 tumor cells. Cancer Res., 45:3541–3547,1985.
16. Dorr, R. T., Bowden, G. T., Alberts, P. S., and Liddil, J. D. Interactions of mitomycin C with DNA detected by alkaline elution. Cancer Res., 45:3510–3516,1985.
17. Fracasso, P. M., and Sartorelli, A. C. Cytotoxicity and DNA lesions produced by mitomycin C and porfiromycin in hypoxic and aerobic EMT6 and Chinese hamster ovary cells. Cancer Res., 46:3939–3944,1986.
18. Rockwell, S. In vivo-in vitro tumor systems: new models for studying the response of tumors to therapy. Lab. Anim. Sci., 27:831–851,1977.
19. Keyes, S. R., Hickman, J. A., and Sartorelli, A. C. The effects of adriamycin on intracellular calcium concentrations of L1210 murine leukemia cells. Eur. J. Cancer Clin. Oncol., 23:295–302,1987.
20. Salmon, S. E., Young, L., Lebowitz, J., Thomson, S., Einspahr, J., Tong, T., and Moon, T. E. Evaluation of an automated image analysis system for counting human tumor colonies. Int J. Cell Cloning, 2:142–160,1984.
21. Kohn, K. W., Ewig, R. A., Erickson, L. C., and Zwelling, L. A. Measurement of strand breaks and cross-links by alkaline elution. In: E. C. Friedbergand and P. C. Hanawalt (eds.), DNA Repair, a Laboratory Manual of Research Procedure, pp. 379–401. New York: Marcel Dekker Inc., 1981.
22. Akman, S., Dietrich, M., Chlebowski, R., Doroshow, J., and Block, J. Menadione (K3) and dicumarol (D) synergy vs. leukemia LI210. Proc. Am. Assoc. Cancer Res., 26:325,1985.
23. Powis, G., Lee See, K., Santone, K. S., Melder, D., and Hodnett, E. M. Quinones as substrates for quinone reductase (NAD(P)H: (quinone-acceptor) oxidoreductase) and the effect of dicumarol on their cytotoxicity. Biochem. Pharmacol., 36: 2473–2477, 1987.
24. Morrison, H., Dimonte, D., Nordenskjold, M., and Jernstrom, B. Induction of cell damage by menadione and benzo{ajpyrene-3,6-quinone in cultures of adult rat hepatocytes and human fibroblasts. Toxicol. Lett., 28:37–43,1985.
25. Talcott, R. E., Rosenblum, M., and Levin, V. A. Possible role of DT-diaphorase in the bioactivation of antitumor quinones. Biochem. Biophys. Res. Commun., III: 346–351,1983.
26. Keyes, S. R., Rockwell, S., and Sartorelli, A. C. Porfiromycin as a bioreductive alkylating agent with selective toxicity to hypoxic EMT6 tumor cells in vivo and in vitro. Cancer Res., 45:3642–3645,1985.
27. Keyes, S. R., Heimbrook, D. C., Fracasso, P. M., Rockwell, S., Sligar, S. G., and Sartorelli, A. C. Chemotherapeutic attack of hypoxic tumor cells by the bioreductive alkylating agent mitomycin C. Adv. Enzyme Regul., 23: 291–307,1985.
28. Rockwell, S., Keyes, S. R., and Sartorelli, A. C. Preclinical studies of porfiromycin as an adjunct to radiotherapy. Radiat Res., 116: 100–113, 1988.
29. Doroshow, J. H. Role of hydrogen peroxide and hydroxyl radical formation in the killing of Ehrlich tumor cells by anticancer quinones. Proc. Natl. Acad. Sci. USA, 83:4514–4518,1986.