Levels Of Free Radical Scavengers Research Articles

Site-specific Oxidative DNA Damage at Polyguanosines Produced by Copper Plus Hydrogen Peroxide

Oxidative DNA damage has been implicated in diverse biological processes including mutagenesis, carcinogenesis, aging, radiation effects, and chemotherapy. We examined the in vitro effect of low concentrations of Cu(II) or H2O2 alone and in combination on supercoiled plasmid DNA. As much as 10(-2) M Cu(II) or 10(-2) M H2O2 alone did not break the DNA. However, a mixture of 10(-6) M Cu(II) plus 10(-5) M H2O2 produced strand breaks and inactivated transforming ability. Strand breakage was proportional to incubation time, temperature, and Cu(II) and H2O2 concentrations. Abasic sites were not detected. Strand breakage was inhibited by metal chelators, catalase, and by high levels of free radical scavengers implying that Cu(II), Cu(I), H2O2, and .OH were involved in the reaction. The extent of DNA strand breakage was not affected by superoxide dismutase indicating that superoxide was not a major contributor to the DNA damage. DNA sequence analysis demonstrated that hot piperidine-sensitive DNA lesions were produced preferentially at sites of 2 or more adjacent guanosine residues. This sequence specificity was observed with Cu(II) plus H2O2 but not with Cu(I) alone. Polyguanosine sequence specificity for DNA damage induction appears to be unique among simple chemical systems. This reaction may be important in mechanisms of oxidative damage in vivo.

Dietary Restriction and Aging: Historical Phases, Mechanisms and Current Directions

Energy intake restriction (ER) without essential nutrient deficiency retards aging and extends life span in all species tested so far, and across wide phylogenetic differences. Historical phases of this model system for studying aging have included modulation of the survival curve, effects on disease susceptibility and effects on physiological indices of aging; the current phase focuses upon possible mechanisms whereby ER influences such widely diverse phenomena. Mechanistic possibilities include effects on the immune system, on basal state and proliferation potential, metabolic rate, DNA repair, levels of free radical scavengers, chromatin structure and protein synthesis and turnover. The ER model may also be useful in analyzing unifactorial versus multifactorial theories of aging, and in clarifying the possible significance of physiological markers that correlate with differences in maximum life spans between species.