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DNA Damage Signaling in Human Skin Cells Exposed to Hexavalent Chromium (pp. 287-304) $100.00
Authors:  (Emil Rudolf, Vera Králová, Ladislava Schroterová, Miroslav Cervinka, Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Králove, Sokolká, Kmil Rudolf, Department of Rheumatology and Clinical Pharmacology, Faculty Teaching Hospital in Hradec Králove, Sokolska, Czech Republic)
Abstract:
Hexavalent chromium (Cr (VI)) is known toxin, mutagen and carcinogen in man. In
addition, exposure to Cr (VI) has been associated with skin irritation, deep ulceration and
cytotoxicity. Intracellular chemistry of Cr (VI) is complex and involves several
enzymatic as well as nonenzymatic reductions resulting in the formation of reactive
chromate intermediates and reactive oxygen species. These endproducts react with DNA
and cause numerous types of lesions which in turn provoke specific signaling pathways
in exposed cells. Although these pathways are generally known, their specific details
concerning individual steps and involved molecules with their respective roles in
biological response of cell populations to this element remain unspecified. 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) dosedependently
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. 


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DNA Damage Signaling in Human Skin Cells Exposed to Hexavalent Chromium (pp. 287-304)