Fluorescence line-narrowing spectrometry: A versatile tool for the study of chemically initiated carcinogenesis

R. Jankowiak, P. Lu, G. J. Small, M. Nishimoto, U. Varanasi, S. K. Kim, N. E. Geacintov

Research output: Contribution to journalArticle

Abstract

An important initiating step in the induction of tumors is believed to be the covalent binding of an active carcinogenic species to a cellular macromolecule, e.g. DNA. Therefore, a spectroscopic technique which allows for positive identification of the intact (macromolecular) DNA adduct and/or isolated damaged nucleosides/nucleotides is highly desirable. It is shown that fluorescence line-narrowing spectroscopy (FLNS) is a rapid, versatile, highly sensitive and selective analytical technique, which can be used directly to characterize DNA adducts and isolated nucleosides. FLNS possesses sufficient resolution to distinguish between the major DNA adducts derived from different enantiomers of benzo[a]pyrene diol-epoxide (BPDE). With the present limit of detection (∼1 adducted base per 108 normal base pairs for 100 μg of DNA), the technique is applicable to in vivo samples. Analysis of liver DNA from fish exposed to benzo[a]pyrene (BP) (100 mg BP/kg fish) showed that a major DNA adduct is derived from syn-BPDE.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume8
Issue number2
DOIs
StatePublished - 1990

Keywords

  • DNA-adduct
  • Fluorescence line-narrowing spectrometry (FLNS)
  • benzo[a]pyrene (BP)
  • benzo[a]pyrene diol epoxide (BPDE)
  • carcinogenesis.

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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