Interplay between genotoxic factors formaldehyde and UV-B exacerbates genome instability in Arabidopsis

Maintenance of genome stability is quintessential feature for all living organisms. The simplest aldehyde formaldehyde and UV-B radiation, two environmental toxic factors, cause DNA damage, affect genome stability, subsequently growth and development across kingdoms. However, the interrelationship of genotoxicity caused by formaldehyde and UV-B remains fragmented in plants. Here, we show that mutants lacking one aldehyde detoxifying enzyme, alcohol dehydrogenase 2 (ADH2, also named GSNOR/FALDH), are hypersensitive to low dosage UV-B radiation or UV-B radiation-mimetic chemical in seedling and root growth. The defects are not caused by the alteration of UV-B sensing, secondary metabolites flavonoid accumulation, or ROS accumulation, rather are UV-B-induced genotoxicity. Increased DNA damage response genes and comet assay tail, cell cycle arrest upon exposure to UV-B provide direct evidence for DNA damage in gsnor mutant. Pharmacological analyses show that the susceptibility to genotoxic stresses is caused by the increased DNA crosslink which results from the enhanced endogenous formaldehyde in gsnor while UV-B promotes the production of formaldehyde. This implies formaldehyde clearance through GSNOR plays a critical role in response to environmental genotoxic stress and interplay between formaldehyde and UV-B exacerbates genome instability.

Deficiency in alcohol dehydrogenase 2 reduces arsenic in rice grains by suppressing silicate transporters

Paddy fields are anaerobic and facilitate arsenite (As(III)) elution from the soil. Paddy-field rice accumulates arsenic (As) in its grains because silicate transporters actively assimilate As(III) during the reproductive stage. Reducing the As level in rice grains is an important challenge for agriculture. Using a forward genetic approach, we isolated a rice (Oryza sativa) mutant, low arsenic line 3 (las3), whose As levels were decreased in aerial tissues, including grains. The low-As phenotype was not observed in young plants before heading (emergence of the panicle). Genetic analyses revealed that a deficiency in alcohol dehydrogenase (ADH) 2 by mutation is responsible for the phenotype. Among the three rice ADH paralogues, ADH2 was the most efficiently produced in root tissue under anaerobic conditions. In wild-type (WT), silicon and As concentrations in aerial tissues increased with growth. However, the increase was suppressed in las3 during the reproductive stage. Accordingly, the gene expression of two silicate transporters, Lsi1 and Lsi2, was increased in WT around the time of heading, whereas the increase was suppressed in las3. These results indicate that the low-As phenotype in las3 is due to silicate transporter suppression. Measurement of intracellular pH by 31P-nuclear magnetic resonance revealed intracellular acidification of las3 roots under hypoxia, suggesting that silicate transporter suppression in las3 might arise from an intracellular pH decrease, which is known to be facilitated by a deficiency in ADH activity under anaerobic conditions. This study provides valuable insight into reducing As levels in rice grains.

Antidotes Against Methanol Poisoning: A Review

Methanol is the simplest alcohol. Compared to ethanol that is fully detoxified by metabolism. Methanol gets activated in toxic products by the enzymes, alcohol dehydrogenase and aldehyde dehydrogenase. Paradoxically, the same enzymes convert ethanol to harmless acetic acid. This review is focused on a discussion and overview of the literature devoted to methanol toxicology and antidotal therapy. Regarding the antidotal therapy, three main approaches are presented in the text: 1) ethanol as a competitive inhibitor in alcohol dehydrogenase; 2) use of drugs like fomepizole inhibiting alcohol dehydrogenase; 3) tetrahydrofolic acid and its analogues reacting with the formate as a final product of methanol metabolism. All the types of antidotal therapies are described and how they protect from toxic sequelae of methanol is explained.