Oxidant injury of cells. DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide (original) (raw)

To determine the biochemical basis of the oxidant-induced injury of cells, we have studied early changes after exposure of P388D, murine macrophages to hydrogen peroxide. Total intracellular NAD+ levels in P388D% cells decreased with H202 concentrations of 40 MM or higher. Doses of H202 between 0.1 and 2.5 mM led to an 80% depletion of NAD within 20 min. With doses of H202 of 250 gM or lower, the fall in NAD and, as shown previously, ATP, was reversible. Higher doses of H202 that cause ultimate lysis of the cells, induced an irreversible depletion of NAD and ATP.