Cloned cytosine deaminase gene expression of Bifidobacterium longum and application to enzyme/pro-drug therapy of hypoxic solid tumors

Biosci Biotechnol Biochem. 2002 Nov;66(11):2362-6. doi: 10.1271/bbb.66.2362.

Abstract

Bifidobacterium longum is a nonpathogenic anaerobic bacterium among normal bacterial flora. Recently, it was reported that B. longum accumulated in hypoxic solid tumors. The gene of interest was expressed in transfected B. longum by the shuttle vector pBLES100 in solid tumors. In this report, we constructed pBLES100-S-eCD, which included the cytosine deaminase gene. We confirmed by western blotting that transfected B. longum produced cytosine deaminase. In addition, transfected B. longum produced cytosine deaminase that converted 5-fluorocytosine into 5-fluorouracil. B. longum could be useful for enzyme/pro-drug therapy of hypoxic solid tumors.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacokinetics*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Bifidobacterium / enzymology*
  • Bifidobacterium / genetics*
  • Bifidobacterium / metabolism
  • Blotting, Western
  • Cloning, Molecular
  • Cytosine Deaminase
  • Flucytosine / pharmacokinetics*
  • Flucytosine / therapeutic use
  • Fluorouracil / pharmacokinetics*
  • Fluorouracil / therapeutic use
  • Gene Expression
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Hypoxia / physiopathology
  • Neoplasms / drug therapy
  • Nucleoside Deaminases / genetics*
  • Nucleoside Deaminases / metabolism*
  • Prodrugs / pharmacokinetics*
  • Prodrugs / therapeutic use
  • Transfection
  • Transformation, Bacterial

Substances

  • Antimetabolites, Antineoplastic
  • Prodrugs
  • Flucytosine
  • Nucleoside Deaminases
  • Cytosine Deaminase
  • Fluorouracil