Do Fanconi anemia genes control cell response to cross-linking agents by modulating cytochrome P-450 reductase activity?

FAE Kruyt*, H Youssoufian

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

9 Citations (Scopus)

Abstract

The Fanconi anemia (FA) genes play an important role in maintaining chromosomal stability and the defense of mammalian cells against cross-linking agents, such as cisplatin and mitomycin C (MMC). Cells derived from FA patients display a characteristic hypersensitivity toward cross-linking agents. Despite great progression in our understanding of the mechanisms that protect cells against these potent anti-cancer drugs, the specific roles of FA gene products in these processes have not been delineated. Recent studies have shown that the FA group C gene product, FANCC, can bind to and regulate the activity of cytochrome P450-reductase (P450R), an enzyme involved in the bioactivation of MMC. In this mini-review, this finding is placed in the context of complex mechanisms involved in the bioreductive activation of MMC acid the hypersensitivity of FA cells to MMC. Although it would be premature to attribute the FA phenotype wholly to an abnormal activation of MMC, the regulation of P450R by FANCC suggests a novel link between one or more FA gene products, the cellular oxidative state, and the response to chemotherapeutic agents.

Original languageEnglish
Pages (from-to)211-215
Number of pages5
JournalDrug Resistance Updates
Volume3
Issue number4
Publication statusPublished - 2000

Keywords

  • C METABOLIC-ACTIVATION
  • MITOMYCIN-C
  • DT-DIAPHORASE
  • NUCLEAR-COMPLEX
  • PROTEINS FANCA
  • CANCER-CELLS
  • KAPPA-B
  • OXYGEN
  • SENSITIVITY
  • FIBROBLASTS

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