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Main Title DNA Adducts of the Antitumor Agent Diaziquone.
Author Gupta, R. C. ; Garg, A. ; Earley, K. ; Agarwal, S. C. ; Lambert, G. R. ;
CORP Author Kentucky Univ., Lexington. ;Environmental Health Research and Testing, Inc., Research Triangle Park, NC.;Environmental Protection Agency, Research Triangle Park, NC. Carcinogenesis and Metabolism Branch.
Publisher c1992
Year Published 1992
Report Number EPA-R-813840, EPA-68-02-4456; EPA/600/J-92/059;
Stock Number PB92-150739
Additional Subjects Antineoplastic agents ; DNA damage ; Toxicity ; Thin layer chromatography ; Nucleotides ; Cross-linking reagents ; Mass spectroscopy ; Phosphorus 32 ; In vitro analysis ; Reprints ;
Library Call Number Additional Info Location Last
NTIS  PB92-150739 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 9p
A study evaluated adduct formation of the antineoplastic agent diaziquone with DNA and nucleotides in vitro. The aziridine moieties of AZQ can be expected to interact covalently with DNA which in turn presumably elicit the antitumor activity. The authors analyzed AZQ-DNA adducts by a modified 32p-postlabeling assay involving purification of the nuclease P1-enriched labeled adducts by high-salt C18 reversed-phase TLC and separation of the eluted adducts on a PEI-cellulose layer using non-urea salt solutions. Modification of calf thymus DNA with AZQ produced two major (22% and 40%) and at least eight minor adducts. At equal concentrations of AZQ and DNA (1 microgram/ul each), peak binding was observed in about 2 h (1,926 plus or minus 378 fmol/microgram DNA) with the binding levels remaining practically unchanged through 4 h. However, incubation for 24 h resulted in over 40% decline, indicating adduct instability. AZQ was found to be highly reactive in vitro as evidenced by its substantial binding (49 plus or minus 14 fmol/microgram DNA) even at a DNA:AZQ ratio of 100:1. When incubated with mononucleotides, AZQ reacted extensively with adenine, guanine, and cytosine but only slightly with thymine.