ABSTRACT
As a nonmutagenic human carcinogen, arsenic (As)'s carcinogenic activity is likely the result of epigenetic changes, particularly alterations in DNA methylation. While increasing studies indicate a potentially important role for timing of As exposure on DNA methylation patterns and the subsequent differential risks for As toxicity and carcinogenesis, there is a lack of research that tackles these critical questions, particularly in human based populations. Here we reported a family-based study including three generations, in which each generation living in the same household had a distinctive timing of As exposure: in adulthood, in utero and during early childhood, and in germlines exposure for grandparents, parents, and grandchildren, respectively. We generated genome-wide DNA methylation data for 18 As-exposed families, nine control families, as well as 18 arsenical skin lesion patients. Our analysis showed that As exposure may leave detectable DNA methylation changes even though exposure occurred decades ago, and the most significant changes of global DNA methylation were observed among patients afflicted with arsenical skin lesions. As exposure across generations shared common differentially methylated DNA loci and regions (744 DML and 15 DMRs) despite the distinctive exposure timing in each generation. Importantly, based on these DML, clustering analysis grouped skin lesion patients together with grandparents in exposed families in the same cluster, separated from grandparents in control families. Further analysis identified a number of DML and several molecular pathways that were significantly distinguished between controls, exposed populations, as well as skin lesion patients. Finally, our exploratory analysis suggested that some of these DML altered by As exposure, may have the potential to be inherited affecting not only those directly exposed but also later generations. Together, our results suggest that common DML and/or DMRs associated with an increased risk for disease development could be identified regardless of when exposure to As occurred during their life span, and thus may be able to serve as biomarkers for identifying individuals at risk for As-induced skin lesions and possible cancers.
Subject(s)
Arsenic Poisoning , Arsenic/toxicity , DNA Methylation , Environmental Exposure , Skin Diseases/chemically induced , DNA Methylation/drug effects , DNA Methylation/genetics , Environmental Exposure/analysis , Environmental Exposure/statistics & numerical data , Family , Female , Humans , Pregnancy , Prenatal Exposure Delayed EffectsABSTRACT
El doctor Luis Prunés fue uno de los grandes maestros de la dermatología chilena. Se formó como dermatólogo en el hospital Saint-Louis en París. En la década 1920 ingresó al Hospital San Luis de Santiago y en 1938 asumió como profesor titular de la cátedra Clínica Universitaria de Piel y Sífilis del Hospital San Vicente de Paul. En 1938 fue el primer presidente de la Sociedad Chilena de Dermato-sifilología. Fue un gran investigador de patologías cutáneas; estudió principalmente la lepra y las lesiones cutáneas asociadas a minerales. Es recordado por preconizar la importancia de la biopsia cutánea. Jubiló en 1954 dejándonos un importante legado dermatológico. El Dr. Prunés recopiló sus mejores casos en más de 20archivos fotográficos, los cuales se encuentran en la biblioteca del Departamento de Dermatología del Hospital Clínico de la Universidad de Chile. El objetivo de este trabajo es presentar parte de su archivo fotográfico, mostrando imágenes impresionantes de tumores cutáneos y lesiones cutáneas inducidas por arsénico.
Dr. Luis Prunés is one of the masters of the Chilean dermatology. He was trained as dermatologist at the Saint-Louis hospital in Paris. Since 1920 he worked as dermatologist at the San Luis Hospital in Santiago and in 1938 he took over as Professor and Chairman of the University Clinic of Skin and Syphilis at San Vicente de Paul Hospital. In 1938, he was the first president of the Chilean Society of Dermatology. He studied leprosy and skin lesions associated with minerals. He is also remembered for advocating the importance of skin biopsy. He retired in 1954, leaving an important legacy. Dr. Prunés compiled his best clinical cases in more than 20 photographic archives, which are located at the Library of the Dermatology Department in the University of Chile Clinical Hospital. The purpose of this paper is to present part of his photographic archive, showing stunning images of large cutaneous tumors and arsenic-induced skin lesions.
