Genome-wide analysis of dichloromethane-regulated genes in human promyelocytic leukemia HL-60 cells

Abstract

Dichloromethane (DCM, methylene chloride) can readily absorb and metabolized to several metabolites in different target organs. Several mutagenesis studies and animal bioassays have been demonstrated the carcinogenicity of DCM. In this present study, we analyze the genome wide expression profiles of DCM using human promyelocytic leukemia HL60 cells. Exposure to IC20 and IC50 doses concentration of DCM altered the expression of 1117 and 1684 up- and also 730 and 1736 down-regulated genes individually, 366 up- and 281 down-regulated genes were commonly expressed. Genes with a significantly altered the expression levels (over 1.5 fold and p-values <0.05) were then classified with gene ontology (GO) and KEGG pathway annotation. Clustering of differentially expressed common genes were associated with JAK-STAT signaling pathway, MAPK signaling pathway, apoptosis, prostate cancer and small cell lung cancer. GO analysis showed the category wise biological process ontology. Functionally important immune response and apoptosis related genes were also validating their expression profiles by quantitative real-time RTPCR. DCM exposure induces IFN-related genes as part of the immune response which was then followed the apoptosis pathway. GO and KEGG pathway database analyses provided a valuable mechanistic insight of DCM exposure in human leukemia cells.