Abstract:
Objective To evaluate the effects of benzene on genes and signal pathways of mouse bone marrow cells using RNA sequencing (RNA-seq), and to provide novel clues for studying potential mechanism of benzene toxicity to bone marrow cells.
Methods C3H/He mice were randomly divided into two groups with ten mice each:control 0mg/(kg· d) and benzene exposure 160 mg/(kg· d) groups. Mice were injected subcutaneously five times per week for four weeks. The separated bone marrow cells were sequenced by RNA-seq technique, and the gene differential expression, enrichment of gene function and signal pathway, and gene co-expression were analyzed.
Results The RNA-seq results showed that there were 227 genes differently expressed after the designed benzene exposure, of which 122 genes were down-regulated and 105 genes were up-regulated. The enrichment analysis results of gene function and signal pathway showed that these differential genes were mainly enriched in immunization, apoptosis, metabolism, oxidative stress, and hematopoietic cell lineage related functions and pathways. The results of gene co-expression analysis showed that there were 14 genes with regulation degrees greater than 10, in which Ccr9, Xaf1, Flt3, and Cd72 were critical genes involved in immunization, apoptosis, hematopoietic cell lineage, and hematopoietic cell differentiation, respectively.
Conclusion Benzene exposure could induce altered transcriptome expression in bone marrow cells in mice and affect immunization, apoptosis, metabolic process, oxidative stress, and hematopoietic cell lineage related functions and pathways. Ccr9, Xaf1, Flt3, and Cd72 might play a key regulatory role in benzene induced hematopoietic toxicity.