Hydrogen peroxide and sequence-specific DNA damage in human cells

Exposure of HeLa cells in monolayer culture to increasing concentrations of exogenously added H2O2 causes damage to cellular DNA. When the DNA is subsequently isolated from the non-apoptotic cells remaining in such cultures, evidence was obtained to suggest that the DNA damage elicited in intact cells was non-random and that certain nucleotide sequences associated with, or related to, the genes for heat shock protein 60 and catalase were more susceptible to damage than others. In contrast, these particular sequences were not specifically susceptible to damage when naked human DNA was exposed directly to H2O2 in vitro. On an overall comparative basis, sequences in the genes encoding catalase, alpha-1 antitrypsin and beta-actin appear more vulnerable to H2O2 in vivo, than sequences in H-ras and the P53 gene which seem surprisingly resistant.