Physiological and Pharmacological Determinants of Sensitivity and Resistance to 5-Fluorouracil in Lower Animals and Man

Bach Ardalan, David Cooney, John S. Macdonald

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The biological activation of 5-fluorouracil (5-FU) is dependent on the operation of several enzymes. These can be aggregated into three principal groups: those that anabolize the drug, those that catabolize it, or its anabolites, and “target” enzymes whose function is finally interrupted following treatment. These families of enzymes are susceptible to two general types of regulation: physiologic control that is used to encompass genetic or biochemical modulation and pharmacologic control that is used to designate the synergistic or antagonistic actions of one drug on the activity of the other. As 5-FU continues to be used in the palliation of breast and gastrointestinal malignancies, more information is being gathered on these classes of enzymes, as well as on the manner in which they are regulated. This chapter discusses selected aspects of such regulation, with emphasis both on published and original findings in the field. Whenever possible, absolute specific activities of the enzymes involved are presented in order that reasonable intercomparisons can be made of their relative contributions to the metabolism of 5-FU.

Original languageEnglish (US)
Pages (from-to)289-321
Number of pages33
JournalAdvances in Pharmacology
Volume17
Issue numberC
DOIs
StatePublished - Jan 1 1980
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology

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