Nitroso-chloramphenicol: possible mediator in chloramphenicol-induced aplastic anemia

A. A. Yunis, A. M. Miller, Z. Salem, M. D. Corbett, G. K. Arimura

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

We compared the effects of CAP and its nitroso derivative on DNA synthesis, CFU-C growth, and cell viability in human bone marrow and on mouse CFU-S viability in vitro. As previously reported from this laboratory, CAP inhibited DNA synthesis only when used in high concentrations (〉3 × 10−4M), and the inhibition was largely reversible. It also caused a reversible concentration-dependent inhibition of CFU-C growth but did not affect marrow cell viability. In sharp contrast, nitroso-CAP inhibited DNA synthesis in much lower concentrations and caused irreversible inhibition of CFU-C growth and cell death at 5 × 10−5M as well as irreversible mouse CFU-S damage. In a rapidly growing human lymphoid cell line, nitroso-CAP caused accumulation of cells in the G2M phase and increasing cell death within the arrested population. We have postulated from these and other observations that CAP-induced aplastic anemia occurs in the predisposed host who provides the milieu for the transformation of the p-NO2 group of the drug to toxic intermediates.

Original languageEnglish (US)
Pages (from-to)36-46
Number of pages11
JournalJournal of Laboratory and Clinical Medicine
Volume96
Issue number1
StatePublished - Jan 1 1980

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Keywords

  • (p-NO)
  • 1
  • 3-bis (2-chloroethyl)1-nitrosourea
  • BCNU
  • CAP
  • CFU-C
  • CFU-S
  • DMEM
  • Dulbecco's modified Eagle's medium
  • HBSS
  • Hanks' balanced salt solution
  • TAP
  • TCA
  • cloramphenicol
  • in vitro myeloid colony-forming cell
  • para-nitro
  • pluripotential hematopoietic stem cell
  • thiamphenicol
  • trichloroacetic acid

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Yunis, A. A., Miller, A. M., Salem, Z., Corbett, M. D., & Arimura, G. K. (1980). Nitroso-chloramphenicol: possible mediator in chloramphenicol-induced aplastic anemia. Journal of Laboratory and Clinical Medicine, 96(1), 36-46.