Abstract 5830: Carcinogenic effects of metal and metalloids through epigenetic reprogramming of human bone marrow stem cells: The bioinformatics database analysis

Abstract

Abstract Many scientific studies showed that the carcinogenic effects of environmental contamination of several metal and metalloids on bone marrow stem cells of human body. These carcinogens include, Cadmium, Mercury, Chromium, Aluminum, Nickel and Arsenic. However, there was no such analysis for elucidating the mechanism of carcinogenic effects and epigenetic reprogramming of human bone marrow stem cells. In this study, we analyzed the carcinogenic effects of mentioned carcinogens, and the mechanism of epigenetic reprogramming using NIH Toxicology Data Network (TOXNET), Comparative Toxico-genomics Database (CTD), AACR Genomics Evidence Neoplasia Information Exchange (GENIE) database, database of Environmental Health Perspectives (EHP), National Institute of Environmental Health Sciences (NIEHS), and other bioinformatics database. We found from CTD analysis that the chemical gene interactions showed highly expressed of 272 common genes with miR140 by Cadmium, Mercury from total 3704 genes (approximately 7% affected genes). The AACR GENIE database analysis showed CDKN3, is associated with bone cancer (2 clinical data), HDAC7, TP53, MAPK3K1, MAP2K2 (8 clinical data) found among 272 genes regulated by Cadmium and Mercury. The CTD analysis showed the chemical gene interactions of highly expressed of 102 common genes with miR140 by Chromium, Mercury from a total of 1406 genes; 268 common genes with CD84, CD226 by Mercury, Nickel from a total of 5032 genes; 103 common genes with CD226 by Aluminum, Mercury from a total of 2556 genes; 248 common genes by Arsenic, Mercury from total 5508 genes. Among these 5508 genes, 248 common genes with ALDHA1, 247 common genes with CD40, 248 common genes with CD44, 247 common genes with CD423, 247 common genes with miR10A by Arsenic, Mercury from total 2556 genes. The epigenetic mechanisms of histone modifications (H3K9me3, H3K27me3, H3K27ac, H3K36me3, H3K4me1, H3K4me3 of B cells, hemopoietic stem cells, mesenchymal bone marrow, and chondrocyte stem cells and miRNAs) and these carcinogens have been revealed by the database of EHP, NIEHS, the NIH Roadmap Epigenomics Mapping Consortium, the National Center for Biotechnology Information (NCBI), and U.S. National Library of Medicine (NLM) database. Our previous study reported that the regulation of epigenetic bivalent histone modifications at transcript starts sequences (TSS) of target genes for heterogenic adult stem cells (CSCs)reprogramming and our current bioinformatics analysis revealed that TP53 is epigenetically reprogrammed with close interaction of thirteen genes by these carcinogens. Therefore, it is important to find the actual epigenetic mechanism both genomic and epigenomic transcriptional regulation and carcinogenic effects of these carcinogens on bone marrow stem cells, and our current study revealed this important relationship. Citation Format: Benedrica Solomon, Richgena Sturrup, Jada Dixon, Kiyona Jackson, Biancaliz Cruz, Charlissia Ferguson, Taylor Walker, Ralph Elisson, Nathan Harris, Jesennia Bonilla, Rose Mary Stiffin, Marilyn Sherman, Alessandra Manzon, Swarnava Das, Madhumita Das, Jayanta Kumar Das. Carcinogenic effects of metal and metalloids through epigenetic reprogramming of human bone marrow stem cells: The bioinformatics database analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5830.