The bystander effect of the nitroreductase/CB1954 enzyme/prodrug system is due to a cell-permeable metabolite.
Hum Gene Ther
; 8(6): 709-17, 1997 Apr 10.
Article
in En
| MEDLINE
| ID: mdl-9113510
ABSTRACT
The bystander effect is an important part of tumor kill using gene-directed enzyme prodrug therapy (GDEPT). Recently, we have described a novel enzyme prodrug system using bacterial nitroreductase and the prodrug CB1954 (NTR/CB1954). We demonstrate here the presence of a cell-permeable cytotoxic activity in the conditioned growth medium of nitroreductase (NTR)-transduced cells treated with CB1954 and show that its appearance corresponds to the appearance of two metabolites of CB1954 previously identified (Friedlos et al., 1992). The degree of bystander effect and the degree of transferred cytotoxicity correlates with the level of NTR enzyme expression. Two other prodrugs for NTR show little bystander killing and do not produce detectable cell permeable metabolites. The elucidation of the mechanism of the bystander effect may allow the more effective use of NTR/CB1954.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aziridines
/
Nitroreductases
/
Prodrugs
/
Genetic Therapy
/
Antineoplastic Agents
Limits:
Animals
Language:
En
Journal:
Hum Gene Ther
Journal subject:
GENETICA MEDICA
/
TERAPEUTICA
Year:
1997
Document type:
Article
Affiliation country:
United kingdom