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Cited by 420

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Metabolism of 5-fluorocytosine to 5-fluorouracil in human colorectal tumor cells transduced with the cytosine deaminase gene: significant antitumor effects when only a small percentage of tumor cells express cytosine deaminase.

Open access
Huber, B E, Austin, E A, Richards, C A, Davis, S T, Good, S S·1994·Proceedings of the National Academy of Sciences

Abstract

The gene encoding cytosine deaminase (CD) has been expressed in the human colorectal carcinoma cell line WiDr. Metabolism studies confirm that tumor cells expressing CD convert the very nontoxic prodrug 5-fluorocytosine (5FCyt) to 5-fluorouracil (5FUra) and 5FUra metabolites. Tumor xenografts composed of CD-expressing cells can selectively generate tumor levels of > 400 microM 5FUra when the host mouse is dosed with nontoxic levels of 5FCyt. The selective metabolic conversion of 5FCyt to 5FUra in CD-expressing tumor cells results in the inhibition of thymidylate synthase and incorporation of 5FUra into RNA. 5FUra is also liberated into the surrounding environment when CD-expressing tumor cells are treated with 5FCyt. The liberated 5FUra is able to kill neighboring, non-CD-expressing tumor cells in vitro and in vivo. Most importantly, when only 2% of the tumor mass contains CD-expressing cells (98% non-CD-expressing cells), significant regressions in all tumors are observed when the host mouse is dosed with nontoxic levels of 5FCyt.

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Metadata

Authors
Huber, B. E., Austin, E. A., Richards, C. A., Davis, S. T., & Good, S. S.
Venue
Proceedings of the National Academy of Sciences
Published
1994-08-16
Volume
91
Issue
17
Pages
8302-8306
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2017593380
Cited by
420
References
1
FWCI
21.35
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Metabolism of 5-fluorocytosine to 5-fluorouracil in human colorectal tumor cells transduced with the cytosine deaminase gene: significant antitumor effects when only a small percentage of tumor cells express cytosine deaminase. https://app.cochat.ai/papers/10.1073/pnas.91.17.8302
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Huber, B. E., Austin, E. A., Richards, C. A., Davis, S. T., & Good, S. S. (1994). Metabolism of 5-fluorocytosine to 5-fluorouracil in human colorectal tumor cells transduced with the cytosine deaminase gene: significant antitumor effects when only a small percentage of tumor cells express cytosine deaminase. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.91.17.8302

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.