| Summary: | Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme deficiency. Our previous study revealed the level of G6PD changed in wild type (WT) mice after benzene exposure. In this study, the pentose phosphate pathway (PPP) in regulation of benzene-induced hematotoxicity was investigated and other potential pathways were discovered in a G6PD deficiency mouse model. WT and G6PD mutation (G6PDmut) mice were exposed to benzene (diluted in corn oil) at doses of 0 and 160 mg/kg by subcutaneous injection for 5 days/week, 4 weeks. Peripheral blood samples and bone marrow cells (BMCs) were obtained and measured. The levels of nicotinamide adenine dinucleotide phosphate (NADPH),reduced glutathione (GSH) and malondialdehyde (MDA) were detected and comet assay was analyzed for DNA damage in BMCs. Finally, RNA sequencing (RNA-seq) of BMCs was performed. The results showed that white blood cells decreased significantly in G6PDmut mice compared with WT mice after benzene treatment. The ratio of hematopoietic stem/progenitor cells significantly decreased in G6PDmut mice exposed to benzene. The reduction of NADPH and GSH revealed the effect on PPP with G6PD deficiency, which then caused the increase of MDA and DNA damage. Finally, RNA-seq results suggested potential genes including SHROOM4, CAMK2B and REN1 played potential roles of G6PD deficiency on benzene-induced hematotoxicity. Renin-angiotensin system and cAMP signaling pathway were potentially involved in the process. Our study provides a better understanding for the effects of G6PD deficiency on benzene-induced hematotoxicity.
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