Bone marrow genotoxicity of 2,5‐dimethylfuran, a green biofuel candidate

Abstract

2,5-Dimethylfuran (DMF) is being considered as a potential green transportation biofuel, but there is limited information about its toxicity and safety. We examined DMF toxicity in the bone marrow using a murine in vitro erythropoietic micronucleus assay and found that exposure to DMF (0.1 mM, 1 hr) induced an increase in micronuclei frequency compared with controls. These data suggest that DMF may be genotoxic to hematopoietic cells and that more thorough toxicological studies on DMF should be conducted to ensure public and occupational safety before it is considered a viable biofuel and produced in mass quantities. As well as specific data on DMF, our study further validates an in vitro cell culture system that captures the essential features of the in vivo mammalian micronucleus genotoxicity assay, enabling increased throughput and controlled studies on hematopoietic DNA damage response, while reducing animal sacrifice. In vitro assays, such as the in vitro micronucleus assay, will be essential as international chemical policy is increasingly utilizing green chemistry principles that require more toxicological testing.

Formaldehyde induces micronuclei in mouse erythropoietic cells and suppresses the expansion of human erythroid progenitor cells

“…We found that FA induced MN in mouse PCEs in a dose-dependent manner. MN in mouse PCEs is a widely used biomarker for genotoxicity (Fromowitz et al, 2012; Hayashi et al, 1994) and MN frequency in human peripheral lymphocytes has been associated with cancer risk (Bonassi et al, 2011). Our finding shows that FA is genotoxic to mouse HSC/HPC in vitro , suggesting that chromosomal damage may be one potential mechanism underlying FA induced leukemogenesis.…”

“…The mouse erythropoietic culture method was detailed previously (Fromowitz et al, 2012; Shuga et al, 2007). In brief, bone marrow (BM) cells were isolated from the hind legs of C57BL/6J mice and were labeled with biotin-conjugated α-Lin Abs, consisting of α-CD3e, α-CD11b, α- CD45R/B220, α-Ly6G/Ly6C, and α-TER-119 Abs (2 µl of each Ab/10 6 cells; BD Pharmingen, San Diego, CA).…”

“…This method forms the basis of an in vitro micronucleus (MN) genotoxicity assay that was found to generate similar results as the widely used in vivo MN genotoxicity assay, thus generating physiologically relevant data (Shuga et al, 2007). Recently, we validated this assay in a study in which we found increased MN frequency in PCEs cultured from mouse bone marrow exposed to 2,5- dimethylfuran (Fromowitz et al, 2012). …”

Phytoremediation for Green Energy

“…Recently however, in vitro studies on erythropoietic micronucleus assay exposed to 0.1 mM DF for an hour, showed an increase in micronuclei, suggesting a genotoxic effect on the bone marrow (Fromowitz et al 2012). Not much is known yet of the toxicity of DMF to human health because of scanty environmental testing.…”

Anin vitrostudy on the genotoxic effect of substituted furans in cells transfected with human metabolizing enzymes: 2,5-dimethylfuran and furfuryl alcohol

“…In vitro exposure to DMF led to the induction of micronuclei in murine bone marrow cells (8). DMF tested negative in the Ames tests (9,10), but tested positive in the rec-assay using Bacillus subtilis bacteria (11).…”