The use of 32P-postlabelling to detect DNA adducts produced by experimental anticancer drugs: DNA-directed nitrogen mustards. 1994

L R Ferguson, and D Siegers, and W A Denny, and A Hewer, and D Phillips
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.

DNA alkylation by four acridine-linked 'DNA-targeted' aniline mustard derivatives has been studied by 32P-postlabelling. P1 nuclease digestion proved much more efficient than butanol extraction for enhancing the yield of adducted bases for these somewhat hydrophilic compounds. The yield of adducts was maximal after approximately 4 h digestion with micrococcal nuclease/spleen phosphodiesterase and remained relatively constant after that up to 24 h, suggesting that the adducts formed are stable under these conditions. There was some variation in the rates of phosphorylation of the adducts by T4 polynucleotide kinase, with optimal labelling generally occurring after 1 h. The (CH2)5O-linked half-mustard derivative 1 gave five nucleotide 3'-diphosphate adduct spots with calf thymus DNA. Two of these were identified as the adenine N1 and N3 adducts, corresponding to those previously identified as the main base adducts formed by 1 following acid digestion studies. The corresponding full mustard also gave five adduct spots. In contrast, the (CH2)3-linked half-mustard 3 gave only two adduct spots, the most intense of which was identified as a guanine adduct. The corresponding full mustard 4 gave three adduct spots, two of which were identified as guanine adducts. These results agree well with those obtained for the same compounds by the more tedious methods of acid digestion to base adducts, followed by isolation on HPLC, and show that the technique of 32P-labelling can be usefully applied to the study of alkylation of DNA by this class of 'targeted' mustards.

UI MeSH Term Description Entries
D010761 Phosphorus Radioisotopes Unstable isotopes of phosphorus that decay or disintegrate emitting radiation. P atoms with atomic weights 28-34 except 31 are radioactive phosphorus isotopes. Radioisotopes, Phosphorus
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D000816 Aniline Mustard Alkylating anti-neoplastic agent. Lymphochin,Lymphocin,Lymphoquin,N,N-Di(2-Chloroethyl)aniline,N,N-bis(2-chloroethyl)aniline,N,N-bis-(2-chloroethyl)aniline,Mustard, Aniline

Related Publications

L R Ferguson, and D Siegers, and W A Denny, and A Hewer, and D Phillips
January 1990, Progress in clinical and biological research,
L R Ferguson, and D Siegers, and W A Denny, and A Hewer, and D Phillips
April 1995, Nucleic acids research,
L R Ferguson, and D Siegers, and W A Denny, and A Hewer, and D Phillips
January 1993, IARC scientific publications,
L R Ferguson, and D Siegers, and W A Denny, and A Hewer, and D Phillips
April 2003, Gut,
L R Ferguson, and D Siegers, and W A Denny, and A Hewer, and D Phillips
January 1993, IARC scientific publications,
L R Ferguson, and D Siegers, and W A Denny, and A Hewer, and D Phillips
January 1993, IARC scientific publications,
L R Ferguson, and D Siegers, and W A Denny, and A Hewer, and D Phillips
August 1994, Cancer letters,
L R Ferguson, and D Siegers, and W A Denny, and A Hewer, and D Phillips
January 1993, IARC scientific publications,
L R Ferguson, and D Siegers, and W A Denny, and A Hewer, and D Phillips
September 1990, Carcinogenesis,
L R Ferguson, and D Siegers, and W A Denny, and A Hewer, and D Phillips
January 1993, IARC scientific publications,
Copied contents to your clipboard!