Mitochondria are important intracellular organelles that produce energy for cellular development, differentiation, and growth. Mitochondrial DNA (mtDNA) presents a 10- to 20-fold higher susceptibility to genetic mutations owing to the lack of introns and histone proteins. The mtDNA repair system is relatively inefficient, rendering it vulnerable to reactive oxygen species (ROS) produced during ATP synthesis within the mitochondria, which can then target the mtDNA. Under conditions of chronic inflammation and excess stress, increased ROS production can overwhelm the antioxidant system, resulting in mtDNA damage. This paper reviews recent literature describing the pathophysiological implications of oxidative stress, mitochondrial dysfunction, and mitochondrial genome aberrations in aging hematopoietic stem cells, bone marrow failure syndromes, hematological malignancies, solid organ cancers, chronic inflammatory diseases, and other diseases caused by exposure to environmental hazards.
DNA, Mitochondrial/*genetics/metabolism ; Hematologic Diseases/genetics/*pathology ; Humans ; *Inflammation ; Mitochondria/genetics ; Mutation ; Neoplasms/genetics/*pathology ; Oxidative Stress ; Reactive Oxygen Species/metabolism

Benzene, a recognized hematotoxicant and carcinogen, can damage the human immune system. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and benzene hematotoxicity in a cross-sectional study of workers exposed to benzene (250 workers and 140 controls). A total of 1,236 tag SNPs in 149 gene regions of six pathways were included in the analysis. Six gene regions were significant for their association with white blood cell (WBC) counts (MBP, VCAM1, ALOX5, MPO, RAC2, and CRP) based on gene-region (P < 0.05) and SNP analyses (FDR < 0.05). VCAM1 rs3176867, ALOX5 rs7099684, and MPO rs2071409 were the three most significant SNPs. They showed similar effects on WBC subtypes, especially granulocytes, lymphocytes, and monocytes. A 3-SNP block in ALOXE3 (rs7215658, rs9892383, and rs3027208) showed a global association (omnibus P = 0.0008) with WBCs even though the three SNPs were not significant individually. Our study suggests that polymorphisms in innate immunity genes may play a role in benzene-induced hematotoxicity; however, independent replication is necessary.
Adult ; Arachidonate 5-Lipoxygenase/genetics/*metabolism ; Benzene/toxicity ; Cell Count ; Cross-Sectional Studies ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Hematologic Diseases/chemically induced/genetics/*metabolism/pathology ; Humans ; Immunity, Innate/genetics ; Leukocytes/*drug effects/metabolism/pathology ; Male ; Occupational Exposure/adverse effects ; Peroxidase/genetics/*metabolism ; Polymorphism, Single Nucleotide ; Vascular Cell Adhesion Molecule-1/genetics/*metabolism