Mechanism of deoxyribonucleic acid breakage induced by 4'-(9-acridinylamino)methanesulfon-m-anisidide and copper: role for cuprous ion and oxygen free radicals

Journal Article · Tue Jun 19 04:00:00 EDT 1984 · Biochemistry; (United States)

OSTI ID:5748526

Wong, A; Huang, C H; Crooke, S T

4-(9-Acridinylamino)methanesulfon-m-anisidide (mAMSA) interacts with Cu(II) ions, as indicated by changes in the mAMSA absorption spectrum induced by Cu(II). The spectral changes are due to the oxidation of mAMSA by Cu(II), resulting in an oxidized mAMSA product and Cu(I). Cu(I) plays an important role in the mAMSA-Cu(II)-induced DNA breakage, since in the presence of neocuproine the DNA breakage is inhibited. Up to 200 ..mu..M, Cu(I) by itself is virtually ineffective, in contrast to the mixture of mAMSA and Cu(II). This suggests that mAMSA, aside from reducing Cu(II) to Cu(I), may play a role in mediating DNA breakage. The DNA breakage was reduced in partially anaerobic conditions, indicating the involvement of molecular oxygen. Catalase and 4,5-dihydroxy-1,2-benzenedisulfonate inhibited the DNA breakage completely, indicating that hydrogen peroxide and superoxide radicals mediate DNA breakage. 1,3-Diazabicyclo(2.2.2)octane partially inhibited the breakage, suggesting that singlet oxygen is involved. The available evidence supports a mechanism indicating the formation of a DNA x mAMSA x Cu(II) ternary complex and the subsequent oxidation-reduction of the complex to form DNA x mAQDI x Cu(I). The oxidation of the complexed Cu(I) may result in reduction of oxygen to oxygen free radicals which induce DNA breaks.

• Research Organization: Baylor College of Medicine, Houston, TX
• OSTI ID: 5748526
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 23:13; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
CATIONS
CHARGED PARTICLES
CHEMICAL REACTIONS
COPPER COMPOUNDS
DATA
DNA
DRUGS
ELEMENTS
EXPERIMENTAL DATA
HYDROPEROXY RADICALS
INFORMATION
IONS
NONMETALS
NUCLEIC ACIDS
NUMERICAL DATA
ORGANIC COMPOUNDS
OXIDATION
OXYGEN
RADICALS
STRAND BREAKS
SUPEROXIDE RADICALS
TRANSITION ELEMENT COMPOUNDS