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In vivo Induction of Poly(ADP‐ribose)polymerase‐1 following Ultraviolet Radiation
Author(s) -
Hayden Brenee S,
Cooper Karen,
Hudson Laurie G.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.836.12
Subject(s) - poly adp ribose polymerase , pyrimidine dimer , in vivo , hairless , dna damage , chemistry , carcinogenesis , parp inhibitor , microbiology and biotechnology , dna repair , polymerase , biochemistry , enzyme , biology , dna , genetics , gene
Skin is a target tissue for arsenic carcinogenesis. Low arsenic concentrations enhance DNA damage and skin tumors in mice following ultraviolet radiation (UVR) exposure, but, the underlying mechanisms are unclear. Inhibition of DNA repair enzymes such as Poly(ADP‐ribose)polymerase (PARP‐1) by arsenic are under investigation, yet little is known about PARP‐1 activation by UVR in the skin. Our aim is to characterize the in vitro and in vivo kinetics and dose dependence of PARP‐1 activation following UVR exposure. Skh‐1 mice (hairless) were exposed to solar simulated UV irradiation (7 kJ/m 2 to 35 kJ/m 2 ). Skin samples were collected from unexposed mice and post exposure, then analyzed for cyclobutane pyrimidine dimers (CPDs) and 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), products of DNA damage, and PARP‐1 activity using immunohistochemistry.CPD formation and PARP‐1 activation were evident at 14 kJ/m 2 . At this UVR dose, CPDs were detected as early as 10 minutes and persisted up to 2 hours post exposure. PARP‐1 activation was maximal at 1 hour and returned to control levels by 4 hours. These experiments reveal conditions for further studies which will focus on the interactions of arsenic and UVR in vivo. This work was supported by NIH award R01 ES015826.