Mitogenomic differences between the normal and tumor cells of colorectal cancer patients

So far, a reliable spectrum of mitochondrial DNA mutations in colorectal cancer cells is still unknown, and neither is their significance in carcinogenesis. Indeed, it remains debatable whether mtDNA mutations are “drivers” or “passengers” of colorectal carcinogenesis. Thus, we analyzed 200 mitogenomes from normal and cancer tissues of 100 colorectal cancer patients. Minority variant mutations were detected at the 1% level. We showed that somatic mutations frequently occur in colorectal cancer cells (75%) and are randomly distributed across the mitochondrial genome. Mutational signatures of somatic mitogenome mutations suggest that they might arise through nucleotide deamination due to oxidative stress. The majority of somatic mutations localized within the coding region (in positions not known from the human phylogeny) and was potentially pathogenic to cell metabolism. Further analysis suggested that the relaxation of negative selection in the mitogenomes of colorectal cancer cells may allow accumulation of somatic mutations. Thus, a shift in glucose metabolism from oxidative phosphorylation to glycolysis may create advantageous conditions for accumulation of mtDNA mutations. Considering the fact that the presence of somatic mtDNA mutations was not associated with any clinicopathological features, we suggested that mtDNA somatic mutations are “passengers” rather than the cause of colorectal carcinogenesis.     

Toxic optic neuropathies: an updated review

Toxic optic neuropathy (TON) is caused by the damage to the optic nerve through different toxins, including drugs, metals, organic solvents, methanol and carbon dioxide. A similar clinical picture may also be caused by nutritional deficits, including B vitamins, folic acid and proteins with sulphur‐containing amino acids. This review summarizes the present knowledge on disease‐causing factors, clinical presentation, diagnostics and treatment in TON. It discusses in detail known and hypothesized relations between drugs, including tuberculostatic drugs, antimicrobial agents, antiepileptic drugs, antiarrhythmic drugs, disulfiram, halogenated hydroquinolones, antimetabolites, tamoxifen and phosphodiesterase type 5 inhibitors and optic neuropathy.