Glycine/glycine N-methyltransferase/sarcosine axis mediates benzene-induced hematotoxicity

Benzene, an important and widely used industrial chemical, is the cause of different types of blood disorders. However, the mechanisms of benzene-induced hematotoxicity are still unclear. This study aimed to explore the effects of benzene on metabolism, especially in amino acid metabolism, in human peripheral blood B lymphocyte cells (AHH-1 cells) treated with 1,4-benzoquinone (1,4-BQ) and in benzene-exposed population based on the untargeted and targeted metabolomics platforms. The results showed that 1,4-BQ disturbed the metabolic activity, such as arginine biosynthesis, citrate cycle, glycine, serine, and threonine metabolism pathways, and significantly upregulated the ratio of sarcosine/glycine in vitro. Meanwhile, the targeted metabolomics further showed that the ratio of sarcosine/glycine was also increased in the benzene exposure population. Notably, the expression of glycine N-methyltransferase (GNMT), an enzyme catalyzing the transformation of glycine to sarcosine, was upregulated both in 1,4-BQ treated AHH-1 cells and benzene-exposed workers. These results imply that the glycine/GNMT/sarcosine axis was involved in benzene-induced hematotoxicity. Such evidence will help to develop a better understanding of the underlying mechanism of benzene-induced hematotoxicity at the level of amino acid metabolism.

Automated summary

The study aimed to explore the effects of benzene on metabolism, especially in amino acid metabolism, in human peripheral blood B lymphocyte cells treated with 1,4-benzoquinone (1,4-BQ) and in benzene-exposed population based on the untargeted and targeted metabolomics platforms. Results showed that 1,4-BQ disturbed metabolic activity, upregulated the ratio of sarcosine/glycine, and implied the involvement of the glycine/GNMT/sarcosine axis in benzene-induced hematotoxicity.