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Evaluating Photogenotoxicity using 3D Tissue Models

Award Number: R43ES025098
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/25/2014
PERIOD OF PERFORMANCE END DATE: 08/31/2016

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Evaluating Photogenotoxicity using 3D Tissue Models - ¿ DESCRIPTION (provided by applicant): The objective of this proposal is to focus on evaluating materials for their ability to cause photogenotoxicity. Photosensitivity is a harmful reaction that occurs when drugs or chemicals in the skin or eyes cause undesirable cellular damage when exposed to UV or visible light. Photogenotoxicity is used as a means to screen a material for its photocarcinogenic potential. Genotoxicity is one of the possible outcomes caused by phototoxins. Although non-photo genotoxicity has standardized testing methods, currently there are no regulatory approved photogenotoxicity assays. Applying the testing procedures used in genotoxicity testing towards photogenotoxicity is not a straightforward approach. In a review of photoclastogenic (UV induced chromosome disruption) compounds, more than 75% of compounds that were classified as photoclastogenic in mammalian assays were negative in the standard 3T3 Neutral Red Update (NRU) phototoxicity assay, demonstrating the high occurrence of pseudophotoclastogenicity. A limitation of many of these assays is the extensive processing of cells to analyze DNA damage, which can require hypotonic cell treatment or cell lysis, DNA fixation or unwinding, staining or electrophoresis, then visual counting and scoring. Cell lines have historically been used in most laboratory studies for genotoxicity assays. Nonetheless, the development of 3D tissue models have allowed for a much greater representation of living tissues. We propose to evaluate in vitro models consisting of hanging drop 3D liver cell culture and 3D reconstructed human epidermal (RHE) tissues. 3D Multi-cell human liver microtissues (InSphero) and 3D differentiated model of the human epidermis (EpiDerm" - MatTek Corp) will be evaluated for their ability to predict photogenotoxins. Evaluation of phosphorylation of histone H2AX will be quantitatively measured as an indicator of DNA damage. DNA damage induces phosphorylation of Ser139 of the carboxy terminus of histone H2AX (¿-H2AX). Detection of ¿-H2AX can be detected by both flow cytometry and immunofluorescence. Monitoring a mechanistic endpoint of DNA repair will allow for a greater accuracy of evaluating Photogenotoxicity by allowing for a more quantitative endpoint.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2014	MILLENNIUM BIORESEARCH, INC.	1765 WENTZ RD	SPINNERSTOWN	PA	18968	BUCKS	USA	Environmental Health	000	1	2/23/2017	NEW	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2014	MB RESEARCH LABORATORIES	1765 WENTZ ROAD	SPINNERSTOWN	PA	18968	BUCKS	USA	Environmental Health	000	1	2/5/2016	NEW	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $133,124 )
2015	2015	MB RESEARCH LABORATORIES	1765 WENTZ ROAD	SPINNERSTOWN	PA	18968	BUCKS	USA	Environmental Health	000	1	2/2/2015	SUPPLEMENT FOR EXPANSION	$133,124
														Subtotal = $133,124

Issue Date FY: 2014 ( Subtotal = $88,608 )
2014	2014	MB RESEARCH LABORATORIES	1765 WENTZ ROAD	SPINNERSTOWN	PA	18968	BUCKS	USA	Environmental Health	000	1	9/25/2014	NEW	$88,608
														Subtotal = $88,608

Grand Total All Awards = $221,732

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Evaluating Photogenotoxicity using 3D Tissue Models

Award Number: R43ES025098

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/25/2014

PERIOD OF PERFORMANCE END DATE: 08/31/2016

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