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

Abstract

4'-(9-Acridinylamino)methanesulfon-m-anisidide (mAMSA) interacts with Cu(II) ion, 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). Two lines of evidence for the oxidation of mAMSA are as follows: (1) The spectral changes induced by manganese oxide, an oxidizing agent, were similar to those induced by Cu(II), and (2) the Cu(II)-induced spectral changes were reversed by a reducing agent, NADPH. Thin-layer chromatographic studies showed the oxidized mAMSA product to be N1-methylsulfonyl-N4-(9-acridinyl)-3-methoxy-2,5-cyclohexadiene-1, 4-diimine (mAQDI). The involvement of Cu(I) in the reaction was demonstrated by the use of two Cu(I)-specific chelating agents, neocuproine and bathocuproine. Neocuproine or bathocuproine chelated the Cu(I) ions in the mixture, producing Cu(neocuproine)2+ complex or Cu(bathocuproine)2+ complex. The stoichiometry of mAMSA-Cu(II) interactions was determined by titrating the mAMSA-Cu(II) mixtures with bathocuproine. Job plots of the absorbance at 480 nm showed a clear end point at a Cu(II)/mAMSA ratio of 1.5/1, indicating that 1.5 equiv of Cu(II) reacts with 1 equiv of mAMSA to produce 1.5 equiv of 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 microM, Cu(I) by itself is virtually ineffective, in contrast to the mixture of mAMSA and Cu(II).(ABSTRACT TRUNCATED AT 250 WORDS)

Resveratrol–Cu(II) induced DNA breakage in human peripheral lymphocytes: Implications for anticancer properties

“…Further, it was also pointed out that several properties of these compounds such as binding to DNA and its degradation are similar to those of known anticancer drugs such as bleomycin, adriamycin and 4 0 -(9-acrdinylamino) methanesulphone-m-anisidine (mAMSA) [18][19][20]. It has been shown that the polyphenolic resveratrol is also capable of strand breakage in DNA in the presence of copper ions [21].…”

“…Earlier studies in our laboratory have established that several antioxidant polyphenolic compounds of plant origin such as flavonoids [15], tannins [16] and curcumins [17] are themselves capable of inducing oxidative DNA damage either alone or in the presence of certain transition metal ions especially Cu(II). Further, it was also pointed out that several properties of these compounds such as binding to DNA and its degradation are similar to those of known anticancer drugs such as bleomycin, adriamycin and 4 0 -(9-acrdinylamino) methanesulphone-m-anisidine (mAMSA) [18][19][20]. It has been shown that the polyphenolic resveratrol is also capable of strand breakage in DNA in the presence of copper ions [21].…”

Strand scission in DNA induced by l‐DOPA in the presence of Cu(II)

“…It is recognized by most workers that hydroxyl radical reactions with DNA are preceded by the association of a complex with DNA, followed by the production of hydroxyl radicals at that particular site [29]. As shown above, L-DOPA is capable of binding to DNA, and if copper ions are available a ternary complex of L-DOPA-Cu(II)-DNA may be formed as in the case of several other ROS generating and DNA cleavage systems [12,30]. Halliwell and co-workers [10] have shown that copper ion concentrations in human brain tissue damaged in Parkinson's disease are at a level that could promote oxidative DNA damage.…”

Release of 2‐Thiobarbituric Acid Reactive Products from Glutamate, Deoxyuridine or DNA during Autoxidation of Dopamine in the Presence of Copper Ions

“…Consistent with our previous observations with hydroquinone and 1,2,4benzenetriol, copper ions are once again demonstrated to be effective in promoting the generation of oxyradicals during dopamine autoxidation and to release aldehydic products from glutamate, deoxyuridine or DNA. Copper ion is known to accelerate drug-induced DNA damage via oxygen free radicals (Wong et al 1983). The inhibition of dopamine-Cu2+ catalyzed formation of TBAR from test substrates by thiourea, catalase and manni-to1 strongly suggests that dopamine was acting through the metal-catalyzed Haber-Weiss reaction in which hydroxyl radicals are produced from H202.…”