Attenuation of DNA Damage in the Dermis and Epidermis of the Albino Hairless Mouse by Chronic Exposure to Ultraviolet-A and -B Radiation¶

Objective: This study determined the effect of purified microcystin-leucine arginine (MC-LR) on biochemical and DNA damage parameters in rats.Methods: Utilization of preparative high-performance liquid chromatography in analysis, purification and collection of MC-LR, then intraperitoneally injection of purified MC-LR to rats. At the end of exposure, animals were sacrificed, and liver cell was isolated to measure the biochemical markers such as superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) as well as measured malondialdehyde (MDA), reactive oxygen species (ROS) and cytochrome P450 (Cyt P450), and DNA damage markers such as comet length, tail length, and tail moment were measured with the single cell gel electrophoresis also called comet assay.Results: The present results showed significantly increased activities of SOD as well as concentration of MDA, ROS with increasing concentration of MC-LR but the activities of CAT and GSH, as well as Cyt P450, were significantly decreased with increasing MC-LR dose while makers of DNA damage such as comet length, tail length, and tail moment also significantly increased with increasing MC-LR dose.Conclusion: This study demonstrated that chronic exposure to MC-LR toxin can induce alteration of biochemical and DNA damage markers.

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Induction of unscheduled DNA synthesis in hairless mouse epidermis by 8-methoxypsoralen plus ultraviolet A(PUVA).

The Journal of Toxicological Sciences ◽

10.2131/jts.26.1 ◽

2001 ◽

Vol 26 (1) ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Masaaki MORI ◽

Hiroshi KOBAYASHI ◽

Yoshio KATSUMURA ◽

Chie FURIHATA

Keyword(s):

Dna Synthesis ◽

Hairless Mouse ◽

Unscheduled Dna Synthesis ◽

Mouse Epidermis ◽

Ultraviolet A

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Senescence of Human Fibroblasts after Psoralen Photoactivation Is Mediated by ATR Kinase and Persistent DNA Damage Foci at Telomeres

Molecular Biology of the Cell ◽

10.1091/mbc.e05-08-0701 ◽

2006 ◽

Vol 17 (4) ◽

pp. 1758-1767 ◽

Cited By ~ 16

Author(s):

Miriam Grosse Hovest ◽

Nicole Brüggenolte ◽

Kijawasch Shah Hosseini ◽

Thomas Krieg ◽

Gernot Herrmann

Keyword(s):

Dna Damage ◽

Human Fibroblasts ◽

Dermal Fibroblasts ◽

Human Dermal Fibroblasts ◽

Ultraviolet A ◽

Cross Link ◽

Telomeric Dna ◽

Histone H2ax ◽

Senescent Phenotype ◽

Atr Kinase

Cellular senescence is a phenotype that is likely linked with aging. Recent concepts view different forms of senescence as permanently maintained DNA damage responses partially characterized by the presence of senescence-associated DNA damage foci at dysfunctional telomeres. Irradiation of primary human dermal fibroblasts with the photosensitizer 8-methoxypsoralen and ultraviolet A radiation (PUVA) induces senescence. In the present study, we demonstrate that senescence after PUVA depends on DNA interstrand cross-link (ICL) formation that activates ATR kinase. ATR is necessary for the manifestation and maintenance of the senescent phenotype, because depletion of ATR expression before PUVA prevents induction of senescence, and reduction of ATR expression in PUVA-senesced fibroblasts releases cells from growth arrest. We find an ATR-dependent phosphorylation of the histone H2AX (γ-H2AX). After PUVA, ATR and γ-H2AX colocalize in multiple nuclear foci. After several days, only few predominantly telomere-localized foci persist and telomeric DNA can be coimmunoprecipitated with ATR from PUVA-senesced fibroblasts. We thus identify ATR as a novel mediator of telomere-dependent senescence in response to ICL induced by photoactivated psoralens.

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