Products from alkylation of DNA in cells by melphalan: human soft tissue sarcoma cell line RD and Escherichia coli WP2

Chemico-biological Interactions
M R OsborneW Warren

Abstract

Alkylation of DNA was studied after treatment with [3H]melphalan (phenylalanine mustard; 1-2 microM) using a human tumour cell line, RD, in culture, or Escherichia coli (WP2 or WP2-uvrA strains) in growth medium. After 6 h at 37 degrees C, treated cells were isolated and re-suspended in fresh growth media. Samples were taken at times up to 48 h for isolation of DNA, and in some cases also RNA and protein (which were found to be alkylated to about the same extent as DNA). Alkylated DNA was analysed as previously described (M.R. Osborne and P.D. Lawley, Chem.-Biol. Interact 89 (1993) 49-60). The four principal products, mono-7-alkylguanine (G-M-OH); mono-3-alkyladenine (A-M-OH); and the cross-linked products G-M-G and A-M-G, were identified in DNA from melphalan treated cells, and quantitatively determined. In each case, alkylation of cellular macromolecules was maximal after about 6 h. In DNA of the human tumour cell line, the relative amounts of adenine products decreased with time, most markedly with A-M-OH to 42% of the 2-h value after 48 h. In DNA of both bacterial strains, A-M-OH was virtually undetectable even at early times. Comparisons between the time course of relative decreases in amounts of these alkylpurine products...Continue Reading

References

Sep 28, 1992·Chemico-biological Interactions·M R Osborne, P D Lawley
Jun 1, 1985·The Australian Journal of Experimental Biology and Medical Science·K MaynardP G Parsons
Dec 1, 1960·The Biochemical Journal·P Brookes, P D Lawley

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Citations

Jul 16, 2008·Analytical and Bioanalytical Chemistry·Dalia Mohamed, Michael Linscheid
Aug 17, 1996·Mutation Research·P D Lawley, D H Phillips
Nov 13, 2008·Cancer Biotherapy & Radiopharmaceuticals·Gauri ShuklaAnil K Mishra
Apr 27, 2007·Archiv der Pharmazie·Anna BielawskaTomasz Anchim
Dec 25, 2007·ChemMedChem·Krzysztof Bielawski, Anna Bielawska
Mar 17, 2006·Journal of Mass Spectrometry : JMS·Michael EdlerMichael Linscheid
Aug 17, 2004·Molecular Pharmacology·Katherine A GouldMichael J Tilby
Mar 6, 2019·Anti-cancer Agents in Medicinal Chemistry·Ghansham S MoreRahul L Gajbhiye
May 4, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Philip WongIan F Tannock

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