Environmental Oxidative Stressors Causing Skin Damage and Carcinogenesis Investigators

Hypochlorous acid (HOCl) is the active oxidizing principle released by standard swimming pool disinfectants used on a global scale, but the health consequences of human exposure inflicted by HOCl (referred to as ‘chlorination stress’) remain largely unknown, posing a major public health concern relevant to populations around the world. Moreover, environmental exposure to solar ultraviolet (UV) radiation is a causative factor in skin photocarcinogenesis.  In an ongoing R21 research project funded by NIEHS since April 2019 (1R21ES029579), Dr. Wondrak, in collaboration with Dr. Watts are exploring the molecular potentiation of UV-induced cutaneous and systemic damage by co-exposure to HOCl-based swimming pool disinfectants, examined in cell culture, skin tissue models, and mouse models of UV-induced skin damage and cancer. In the Wondrak laboratory, organotypic models of fully differentiated human epidermis are treated with topical HOCl at low micromolar concentrations, a procedure mimicking chlorination exposure experienced by recreational swimmers. Performing gene expression analysis in collaboration with the SWEHSC Genomics Core facility, TXNRD2, a gene encoding the mitochondrial antioxidant enzyme thioredoxin reductase 2, has now been identified as a novel key response factor in human skin, determining sensitivity to recreational chlorination stress.

 

Relevance to SWEHSC: 

Dr. Watts’ research entails development of protocols, standards and methods for detecting and quantitating microbes from diverse sample types, including environmental samples. The approach for microbial analysis involves isolation of DNA followed by metagenomic next-generation sequencing (mNGS) followed by rapid data analysis methods to identify organisms present in the sample and their relative abundances. Dr. Watts was first author on a 2019 publication in PLoS Computational Biology1 reporting on data analysis methods in defined microbial communities and clinical samples.

Examinations of the pathological role of oxidative and proteotoxic stress in skin carcinogenesis and solar photodamage are underway. In a seminal 2015 research paper, the Wondrak and Zhang labs have successfully identified the most potent endogenous UVA-photosensitizer and aryl hydrocarbon receptor (AhR) agonist ever described in human skin, research that was the subject of a specialized editorial review article. They have also designed novel heat shock response-directed therapeutics for the apoptotic elimination of malignant melanoma cells, and have identified the apocarotinoid bixin as the first photo-chemopreventive biofactor and sunburn blocker, derived from the dietary food pigment annato consumed all over Latin America since Precolumbian times.

 

Cluster of Efforts: 

Wondrak, D. Zhang,  Watts

 

SWEHSC Terms: