Abstract
The lack of highly exploitable biochemical differences between normal tissues and some tumors can theoretically be circumvented by a strategy utilizing gene insertion prophylactically to create tissue mosaicism for drug sensitivity, thereby ensuring that any tumor arising clonally will differ from part of the normal cell population. Elements of the strategy were tested with neoplastic BALB/c murine cell lines bearing the herpes thymidine kinase gene. Exposure to the herpes thymidine kinase-specific substrate 9-{[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl}guanine ablated the clonogenic potential of the cells in vitro, and administration of this drug to BALB/c mice bearing tumors produced by the cell lines uniformly induced complete regression of the tumors. The observed responses to therapy imply that the strategy may prove valuable when the genetic technology needed for its human implementation becomes available.
Footnotes
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↵1 Supported by a Clinical Investigator Award from the United States Veterans Administration.
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↵2 To whom requests for reprints should be addressed, at Veterans Administration Medical Center (151), 200 Springs Road, Bedford, MA 01730. This is Publication 131 of the Hubert H. Humphrey Cancer Research Center at Boston University.
- Received February 25, 1986.
- Revision received June 10, 1986.
- Accepted June 27, 1986.
- ©1986 American Association for Cancer Research.
Volume 46, Issue 10
