Genotoxicity of photoilluminated riboflavin in the presence of Cu(II).
Riboflavin is known to generate superoxide anion (O2.-) and other reactive oxygen species in the presence of Cu(II) and light as well as cause fragmentation of DNA and protein in vitro. In the present study we examined the genotoxic effects of photoilluminated riboflavin in the presence of Cu(II). Using the phage inactivation assay, a significant decline in plaque-forming unit (PFU) is seen. Results of Ames testing have suggested that probably a frameshift mutation is caused by a riboflavin-Cu(II)-mediated reaction. Using neocuproine as a Cu(I) sequestering reagent, Cu(I) has been shown to be an essential intermediate generated in the reaction between Cu(II), photoilluminated riboflavin, and DNA. Results obtained with various scavengers of active oxygen species strongly suggest that the species predominantly responsible for DNA damage is oxygen (O2) in the singlet or triplet state, together with H2O2, hydroxyl radical, and hydroxyl ion, to a lesser extent. In the case of riboflavin, a ternary complex of DNA-drug-Cu(II) is presumably formed. A redox reaction, involving riboflavin and Cu(II) in the complex, may then occur with the formation of a DNA-oxidized riboflavin-Cu(I) complex. This probably acts as a catalyst for the oxidation of Cu (I) to Cu(II), during which molecular oxygen is reduced to generate a variety of active oxygen species. The probable mechanism for the generation of these reactive oxygen species has also been proposed.
Jazzar
M M
MM
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, India.
Naseem
I
I
D010582:Bacteriophage lambda / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D003300:Copper; D004249:DNA Damage; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D005819:Genetic Markers; D008027:Light; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011506:Proteins / Q000187:drug effects; D012256:Riboflavin / Q000528:radiation effects* / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects
D005819:Genetic Markers; D009153:Mutagens; D011506:Proteins; D003300:Copper; D012256:Riboflavin