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DNA damage and repair of human skin keratinocytes concurrently exposed to pyrene derivatives and UVA light

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Toxicology Research Vol - 2 Issue - 2

Toxicology Research Vol - 2 Issue - 1

Toxicology Research Vol -1

DNA damage and repair of human skin keratinocytes concurrently exposed to pyrene derivatives and UVA light

Content Provider	Royal Society of Chemistry (RSC)
Author	Yu, Hongtao Fullove, Tracie Perkins
Copyright Year	2013
Abstract	Polycyclic aromatic hydrocarbons (PAHs), a class of mutagenic environmental contaminants, induce toxicity through both metabolic activation and light irradiation. Pyrene, one of the most widely studied PAHs, along with its mono-substituted derivatives, 1-amino, 1-bromo, 1-hydroxy, and 1-nitropyrene, were chosen to study the effect of substituents on their phototoxicity, DNA damage and repair. Both alkaline Comet assay, which detects direct DNA damage, and Fpg endonuclease Comet assay, which detects oxidative DNA damage, were conducted at 0, 2, 4, 8, and 24 h of incubation of the cells in a minimal growth medium after concomitant exposure to pyrene derivatives and UVA light. All these compounds are photocytotoxic and the phototoxicity is both incubation time and PAH dose dependent; whereas those without light are not toxic. The LC50 obtained are in the range of 3.5–9.3 μM. Cellular DNA damage, both direct and oxidative, is observed immediately after the cells are treated with UVA light and the pyrene derivatives at a concentration of 1.0 μM. The amount of DNA damage (both direct and oxidative) increases from 0 to 4 h of incubation. After 4 hours, subsequent damage induction declines, and this is perceived to be mainly through DNA repair. After longer incubation of 8 h, the damaged cellular DNA starts to be repaired, resulting in a greatly reduced amount of DNA damage, and the DNA damage reaches the minimum at 24 h of incubation. 1-Aminopyrene and 1-hydroxypyrene cause more DNA oxidative damage immediately after the exposure (0 h of incubation), and these damages are repaired within the same timeframe as the other tested compounds. The oxidative DNA damage caused by 1-bromopyrene is repaired starting at 2 h of incubation, earlier than the damage caused by all the other compounds.
Starting Page	193
Ending Page	199
Page Count	7
File Format	HTM / HTML PDF
ISSN	2045452X
Volume Number	2
Issue Number	3
Journal	Toxicology Research
DOI	10.1039/c3tx20085j
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	UVA Polycyclic aromatic hydrocarbon Direct DNA damage Ultraviolet DNA repair Comet assay Pyrene DNA 1-Hydroxypyrene 1-Nitropyrene Phototoxicity Median lethal dose Endonuclease
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Toxicology

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