Abstrakt
The purpose of this study was to investigate the initial stages of Cr (VI)-induced DNA damaging in normal human skin fibroblasts. Primary human skin fibroblasts were exposed to Cr (VI) at a concentration range of 1-50 ?M during 24 h.
Our results confirm that Cr (VI) dose-dependently stimulates both directly (via its reactive metabolic intermediates) and indirectly (through generated oxidative stress) DNA damaging which results in the activation of DNA damage response pathway during 24 h of treatment. The important members of this pathway include ATM/ATR kinases which stimulate their downstream targets Chk1, Chk2 and p53 in mediating transient G2/M cell cycle arrest and activating cell death characterized by the specific cleavage of PARP.
Inhibition of ATM/ATR pathway and suppresion of oxidative stress in exposed cells significantly suppressed cell damage characterized by specific PARP cleavage.