Bone Marrow Oxidative Stress and Acquired Lineage-Specific Genotoxicity in Hematopoietic Stem/Progenitor Cells Exposed to 1,4-Benzoquinone

• Published in: International journal of environmental research and public health 2020-08, Vol.17 (16), p.5865
• Main Authors: Mathialagan, Ramya Dewi, Abd Hamid, Zariyantey, Ng, Qing Min, Rajab, Nor Fadilah, Shuib, Salwati, Binti Abdul Razak, Siti Razila
• Format: Article
• Language: English
• Subjects: Animals; Benzene; Benzoquinone; Benzoquinones - toxicity; Bone Marrow; Bone Marrow Cells; Carbonyl compounds; Carbonyls; Cell culture; Cell cycle; Cells (biology); Cytokines; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - drug effects; Epigenetics; Exposure; Genotoxicity; Growth factors; Hematology; Hematopoietic stem cells; Hematopoietic Stem Cells - drug effects; Homeostasis; Hydrocarbons; Laboratory animals; Malondialdehyde; Metabolism; Metabolites; Mice; Oxidation; Oxidative Stress; Progenitor cells; Proteins; Stem cells; Studies; Superoxide dismutase; Tails
• ISSN: 1660-4601; 1661-7827; 1660-4601
• DOI: 10.3390/ijerph17165865

Hematopoietic stem/progenitor cells (HSPCs) are susceptible to benzene-induced genotoxicity. However, little is known about the mechanism of DNA damage response affecting lineage-committed progenitors for myeloid, erythroid, and lymphoid. Here, we investigated the genotoxicity of a benzene metabolite, 1,4-benzoquinone (1,4-BQ), in HSPCs using oxidative stress and lineage-directed approaches. Mouse bone marrow cells (BMCs) were exposed to 1,4-BQ (1.25-12 μM) for 24 h, followed by oxidative stress and genotoxicity assessments. Then, the genotoxicity of 1,4-BQ in lineage-committed progenitors was evaluated using colony forming cell assay following 7-14 days of culture. 1,4-BQ exposure causes significant decreases ( < 0.05) in glutathione level and superoxide dismutase activity, along with significant increases ( < 0.05) in levels of malondialdehyde and protein carbonyls. 1,4-BQ exposure induces DNA damage in BMCs by significantly ( < 0.05) increased percentages of DNA in tail at 7 and 12 μM and tail moment at 12 μM. We found crucial differences in genotoxic susceptibility based on percentages of DNA in tail between lineage-committed progenitors. Myeloid and pre-B lymphoid progenitors appeared to acquire significant DNA damage as compared with the control starting from a low concentration of 1,4-BQ exposure (2.5 µM). In contrast, the erythroid progenitor showed significant damage as compared with the control starting at 5 µM 1,4-BQ. Meanwhile, a significant ( < 0.05) increase in tail moment was only notable at 7 µM and 12 µM 1,4-BQ exposure for all progenitors. Benzene could mediate hematological disorders by promoting bone marrow oxidative stress and lineage-specific genotoxicity targeting HSPCs.