Deoxyribonucleic acid breaks produced by 4'-(9-acridinylamino)methanesulfon-m-anisidide and copper
It has been demonstrated that 4'-(9-acridinylamino)methanesulfon-m-anisidide (mAMSA), in the presence of Cu(II) ion, causes the breakage of plasmid pDPT275 and pBR322 superhelical form I DNA. In neutral pH, the degradative product was nicked, relaxed form II DNA, resulting from single-stranded DNA breakage. The extent of DNA breakage was both mAMSA concentration and Cu(II) concentration dependent. DNA breakage increased with increasing time of drug treatment. The mAMSA-Cu(II)-induced DNA breakage varied with pH values and also with the nature of the buffer systems. The interaction of Cu(II) with mAMSA was examined by using absorption and fluorescence spectroscopies. Interaction of Cu(II) with mAMSA was characterized by a decrease in the absorption at 435 and 420 nm with a simultaneous increase at 330 nm. A highly fluorescent product was obtained upon reacting mAMSA with Cu(II), with an emission spectrum (excitation at 400 nm) showing a doublet at 430 and 450 nm and a shoulder around 480 nm. The spectral changes are also dependent similarly on the pH and the nature of buffer. Other divalent metal ions such as Co(II), Cd(II), Ni(II), and Zn(II) do not induce DNA breakage or spectral changes. The oAMSA isomer, which has no antitumor activity, is less effective in inducing DNA breakage than the mAMSA.
- Research Organization:
- Baylor College of Medicine, Houston, TX
- OSTI ID:
- 5748544
- Journal Information:
- Biochemistry; (United States), Vol. 23:13
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTINEOPLASTIC DRUGS
TOXICITY
COPPER
DNA
STRAND BREAKS
ABSORPTION SPECTROSCOPY
BIOLOGICAL PATHWAYS
BUFFERS
COMPARATIVE EVALUATIONS
EXPERIMENTAL DATA
FLUORESCENCE SPECTROSCOPY
PH VALUE
TIME DEPENDENCE
DATA
DRUGS
ELEMENTS
EMISSION SPECTROSCOPY
INFORMATION
METALS
NUCLEIC ACIDS
NUMERICAL DATA
ORGANIC COMPOUNDS
SPECTROSCOPY
TRANSITION ELEMENTS
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)