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DNA Damage Signaling in Human Skin Cells Exposed to Hexavalent Chromium

Publication at Faculty of Medicine in Hradec Králové |
2009

Abstract

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 µM 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.