Nitroreductase-mediated cell ablation is very rapid and mediated by a p53-independent apoptotic pathway

Gene Therapy

Volumn 6, Issue 5, 1999, Pages 764-770

  Cui, W ^a   Gusterson, B ^b   Clark, A J ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

CB1954; Cell ablation; Nitroreductase; p53

Indexed keywords

5 (1 AZIRIDINYL) 2,4 DINITROBENZAMIDE; NITROREDUCTASE; PRODRUG; PROTEIN P53;

ANIMAL EXPERIMENT; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; FEMALE; GENE TARGETING; INTRAPERITONEAL DRUG ADMINISTRATION; MAMMARY GLAND; MOUSE; NONHUMAN; PRIORITY JOURNAL; TRANSGENIC MOUSE;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; AZIRIDINES; FEMALE; GENE THERAPY; GENES, P53; IMMUNOHISTOCHEMISTRY; IN SITU NICK-END LABELING; MAMMARY GLANDS, ANIMAL; MICE; MICE, TRANSGENIC; NEOPLASMS; NITROREDUCTASES; PRODRUGS; TIME FACTORS;

ANIMALIA; MUS MUSCULUS;

EID: 0032981046     PISSN: 09697128     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.gt.3300873     Document Type: Article

References (24)

1. Moolten FL. Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res 1986; 46: 5276-5281.
2. Moolten FL, Wells JM, Heyman RA, Evans RM. Lymphoma regression induced by ganciclovir in mice being a herpes thymidine kinase transgene. Hum Gene Ther 1990; 1: 125-135.
3. Chambers R et al. Comparison of genetically engineered herpes simplex viruses for the treatment of brain tumors in a scid mouse model of human malignant glioma. Proc Natl Acad Sci USA 1995; 92: 1411-1415.
4. Black ME, Newcomb TG, Wilson HMP, Loeb LA. Creation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy. Proc Natl Acad Sci USA 1996; 93: 3525-3529.
5. Izquierdo M et al. Human malignant brain tumor response to herpes simplex thymidine kinase (HSVtk)/ganciclovir gene therapy. Gene Therapy 1996; 3: 491-495.
6. Borrelli E et al. Transgenic mice with inducible dwarfism. Nature 1989; 339: 538-541.
7. Canfield V, West AB, Goldenring JR, Levenson R. Genetic ablation of parietal cells in transgenic mice: a new model for analyzing cell lineage relationships in the gastric mucosa. Proc Natl Acad Sci USA 1996; 93: 2431-2435.
8. Cheng C et al. Unique spectrum of activity of 9-[(1,3-dihydroxy-2-propoxy)methyl]-guanine against herpesviruses in vitro and its mode of action against herpes simples virus type 1. Proc Natl Acad Sci USA 1983; 80: 2767-2770.
9. Clark AJ et al. Selective cell ablation in transgenic mice expressing E. coli nitroreductase. Gene Therapy 1997; 4: 101-110.
10. Bridgewater JA et al. Expression of nitroreductase enzyme in mammalian cells renders them selectively sensitive to killing by the prodrug CB1954. Eur J Cancer 1995; 31A: 2362-2370.
11. Drabek D, Guy J, Craig R, Grosveld F. The expression of bacterial nitroreductase in transgenic mice results in specific cell killing by the prodrug CB1954. Gene Therapy 1997; 4: 111-118.
12. Knox RJ, Friedlos F, Boland M. The bioactivation of CB1954 and its use as a prodrug in antibody directed enzyme pro-drug therapy. Cancer Metast Rev 1993; 12: 195-212.
13. Wallace H, McLaren K, Al-Shawi R, Bishop JO. Consequences of thyroid hormone deficiency induced by the specific ablation of thyroid follicle cells in adult transgenic mice. J Endocrinol 1994; 143: 107-120.
14. Bridgewater JA et al. The bystander effect of the nitroreductase/CB1954 enzyme/prodrug system is due to a cell-permeable metabolite. Hum Gene Ther 1997; 10: 709-717.
15. Ko LJ, Prives C. p53: Puzzle and paradigm. Genes Dev 1996; 10: 1054-1072.
16. Lowe SW et al. p53 is required for radiation induced apoptosis in mouse thymocytes. Nature 1993; 362: 847-849.
17. Clarke AR et al. Thymocyte apoptosis induced by p53 dependent and independent pathway. Nature 1993; 362: 849-852.
18. Gusterson B et al. Selective cell ablation in the mammary gland of transgenic mice. Endocrine-Related Cancer 1997; 4: 67-74.
19. Greenblatt M, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 1994; 54: 4855-4878.
20. Bursh W, Kleine L, Tenniswood M. Biochemistry of cell death by apoptosis. Biochem Cell Biol 1990; 68: 1071-1074.
21. El-Deiry WS et al. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 1994; 54: 1169-1174.
22. Lowe SW et al. p53 status and the efficacy of cancer therapy in vivo. Science 1994; 266: 807-810.
23. Kasan MB et al. Participation of p53 in the cellular response to DNA damage. Cancer Res 1991; 51: 6304-6311.
24. Malcomson RG et al. Apoptosis induced by γ-irradiation, but not CD4 ligation, of peripheral T lymphocytes in vivo is p53-dependent. J Pathol 1997; 181: 166-171.