Detection of adriamycin-DNA adducts by accelerator mass spectrometry.

Kate Coldwell, Suzanne M. Cutts, Ted J. Ognibene, Paul Henderson, Don R. Phillips

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

There have been many attempts in the past to determine whether significant levels of Adriamycin-DNA adducts form in cells and contribute to the anticancer activity of this agent. Supraclincal drug levels have been required to study drug-DNA adducts because of the lack of sensitivity associated with many of the techniques employed, including liquid scintillation counting of radiolabeled drug. The use of accelerator mass spectrometry (AMS) has provided the first direct evidence of Adriamycin-DNA adduct formation in cells at clinically relevant Adriamycin concentrations. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection (compared to liquid scintillation counting) and has revealed adduct formation within an hour of drug treatment. The rigorous protocol required for this approach, together with many notes on the precautions and procedures required in order to ensure that absolute levels of Adriamycin-DNA adducts can be determined with good reproducibility, is outlined in this chapter.

Original languageEnglish (US)
Pages (from-to)103-118
Number of pages16
JournalMethods in molecular biology (Clifton, N.J.)
Volume613
StatePublished - 2010
Externally publishedYes

Fingerprint

DNA Adducts
Mass Spectrometry
Scintillation Counting
Pharmaceutical Preparations
Antineoplastic Agents
Doxorubicin
doxorubicin-DNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Coldwell, K., Cutts, S. M., Ognibene, T. J., Henderson, P., & Phillips, D. R. (2010). Detection of adriamycin-DNA adducts by accelerator mass spectrometry. Methods in molecular biology (Clifton, N.J.), 613, 103-118.

Detection of adriamycin-DNA adducts by accelerator mass spectrometry. / Coldwell, Kate; Cutts, Suzanne M.; Ognibene, Ted J.; Henderson, Paul; Phillips, Don R.

In: Methods in molecular biology (Clifton, N.J.), Vol. 613, 2010, p. 103-118.

Research output: Contribution to journalArticle

Coldwell, K, Cutts, SM, Ognibene, TJ, Henderson, P & Phillips, DR 2010, 'Detection of adriamycin-DNA adducts by accelerator mass spectrometry.', Methods in molecular biology (Clifton, N.J.), vol. 613, pp. 103-118.
Coldwell, Kate ; Cutts, Suzanne M. ; Ognibene, Ted J. ; Henderson, Paul ; Phillips, Don R. / Detection of adriamycin-DNA adducts by accelerator mass spectrometry. In: Methods in molecular biology (Clifton, N.J.). 2010 ; Vol. 613. pp. 103-118.
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