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Endogenous HOCl-derived chloramines in skin inflammation and photocarcinogenesis

Award Number: R21CA299160
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/19/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Endogenous HOCl-derived chloramines in skin inflammation and photocarcinogenesis - PROJECT SUMMARY / ABSTRACT Human skin is ubiquitously exposed to solar ultraviolet (UV) radiation, other environmental toxicants, and combinations thereof. Solar radiation is a potent environmental human carcinogen. Cutaneous exposure to solar ultraviolet (UV) radiation is a causative factor in skin photocarcinogenesis, and nonmelanoma skin cancer (NMSC) is the most common malignancy in the United States with increasing incidence, a public health burden of considerable magnitude. In search of relevant environmental co-exposures that might modulate skin stress responses to solar UV, we have focused recently on skin chlorination, a largely understudied environmental exposure in the context of drinking water and recreational freshwater disinfection operative on a global scale. Our unpublished research has identified a novel chlorination product, chloro-cis-urocanic acid (Cl-cis-UCA), detectable in human skin upon co-exposure to solar UV and HOCl. Trans-urocanic acid (trans-UCA) is a major filaggrin-derived skin chromophore undergoing photoisomerization upon exposure to solar UV causing the formation of the bio-active mediator cis-urocanic acid (cis-UCA) in human skin. Even though a critical role of cis- UCA in the modulation of skin photodamage, photoimmunosuppression, and photocarcinogenesis is firmly established, occurrence and function of the novel UCA-derivative Cl-cis-UCA remain undefined. In this exploratory R21 project entitled ‘Endogenous HOCl-derived chloramines in skin inflammation and carcinogenesis’ we propose investigations focusing on this novel, heretofore unrecognized skin chloramine component (Cl-cis-UCA), formed uniquely upon co-exposure to solar UV and environmental chlorination stress. Our goal of investigating its cutaneous occurrence and potential role in skin photodamage, photoimmunosuppression, and photocarcinogenesis is pursued as follows: Aim #1 explores occurrence and function of Cl-cis-UCA in organotypic human epidermal reconstructs exposed to the isolated and combined action of solar UV and environmental chlorination stress. The analytical method pursued here is based on non- invasive tape stripping followed by Cl-cis-UCA detection amenable to rapid human translation. Aim #2 explores the role of Cl-cis-UCA exposure in established murine models of solar UV-induced photodamage (sunburn and inflammation), systemic photoimmunosuppression, and photocarcinogenesis. Given the ubiquitous nature of solar UV and chlorination stress co-exposure experienced by human skin worldwide, examining formation and function of the novel skin chlorination photoproduct Cl-cis-UCA in relevant skin models of photodamage and photocarcinogenesis addresses an urgent need to define the role of this intermediate in human skin originating from a ubiquitous environmental co-exposure. Based on our novel analytical approach and functional studies, Cl-cis-UCA might be recognized to play a role as a novel exposure biomarker, molecular target, and mediator of cutaneous responses relevant to human skin.


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: 2026 ( Subtotal = $399,712 )
2026	2026	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Cause and Prevention Research	000	1	5/19/2026	NEW	$399,712
														Subtotal = $399,712

Grand Total All Awards = $399,712

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Endogenous HOCl-derived chloramines in skin inflammation and photocarcinogenesis

Award Number: R21CA299160

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/19/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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