Reactive oxygen species, produced endogenously or by exposure to environmental chemicals and ionizing radiation, induce a wide range of DNA lesions. The variety of chemistries associated with different oxidants suggests that each will produce a unique spectrum of DNA damage products. To extend our efforts to relate genotoxin chemistry to DNA damage, we measured both strand breaks and 8-oxoguanine (8-oxoG) in DNA after exposure to gamma-radiation, Fe(II)-EDTA/H2O2, Cu(II)/H2O2, and peroxynitrite at concentrations approaching physiological relevance. We found that the ratio of 8-oxoG to strand breaks varied more than 10-fold depending on the oxidizing agent: approximately 0.4 for Cu(II)/H2O2 and peroxynitrite and approximately 0.03 for Fe-(II)-EDTA/ H2O2 and gamma-radiation. In the case of Cu(II)/H2O2, the relative proportion of 8-oxoG and strand breaks was found to vary more than 2-fold (0.14-0.37) for different Cu(II) concentrations, consistent with other studies. We were able to detect 8-oxoG formation by peroxynitrite by using low peroxynitrite concentrations in conjunction with a sensitive immunoaffinity/HPLC-ECD methodology. The level of 8-oxoG relative to strand breaks produced by peroxynitrite was higher than that produced by Fe(II)-EDTA/H2O2 and gamma-radiation, which is consistent with the altered reactivity or accessibility of a non-hydroxyl radical species produced by peroxynitrite.
Chromium(VI) is a known human carcinogen which requires intracellular reduction for activation. Ascorbate (vitamin C) has been reported to function as a major reductant of Cr(VI) in animals and cell culture systems. The reaction of Cr(VI) with varying concentrations of ascorbate was studied under physiological conditions in vitro in order to determine the types of reactive intermediates produced and to evaluate the reactivity of these intermediates with DNA. Reactions of 1.8 mM Cr(VI) with 0-18 mM ascorbate at pH 7.0 in N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid (HEPES; 0.10 M) and tris(hydroxymethyl)aminomethane hydrochloride (Tris.HCl; 0.050 M) buffers were studied by electron paramagnetic resonance and UV/visible spectroscopy. Cr(V) and carbon-based free radical adducts of 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) were observed at 0.5 to 1 and 1 to 1 reactions of ascorbate to Cr(VI). Levels of Cr(V) were higher for reactions in HEPES buffer, and levels of carbon-based radicals were higher in Tris.HCl buffer. Levels of Cr(IV) and Cr(III) increased with increasing concentration of ascorbate in both buffers. Reaction of Cr(VI) with varying ascorbate in the presence of calf thymus DNA or pBR322 DNA resulted in Cr-DNA adducts and plasmid relaxation, respectively. Maximum binding of Cr to DNA was observed for the 1:1 reaction ratio of Cr(VI) with ascorbate in both HEPES and Tris.HCl buffers, but total Cr bound to DNA was 8-fold lower in Tris.HCl than HEPES buffer. Preincubation of Cr(VI) with ascorbate before reaction with DNA decreased Cr-DNA binding to background levels. Preincubation of Cr(III) with ascorbate resulted in only low Cr-DNA binding. Levels of Cr-DNA binding were higher with single-stranded vs double-stranded DNA. Reactions with 14C-labeled ascorbate produced no cross-linking of ascorbate to DNA. Maximum plasmid relaxation was observed for the 1:1 ascorbate to Cr(VI) ratio in both buffers; however, single-strand breaks were 2-fold higher in Tris.HCl than HEPES buffer. Reactions with plasmid in the presence of DMPO quenched formation of single-strand breaks. Interpretation of these results in light of the spectroscopic studies suggested that Cr(V) and carbon-based radicals were responsible for Cr-DNA adducts and DNA single-strand breaks, respectively.
Objectives To demonstrate the feasibility of continuing cochlear implantation during the coronavirus disease 2019 crisis and to report on trends of referrals via the neonatal hearing screening programme. Methods A prospective case series was conducted on children who underwent cochlear implantation during the coronavirus disease 2019 crisis in the UK and a sample of referrals via the neonatal hearing screening programme. A step-by-step description of peri-operative management is included. Results Regionally, between February and May 2020, 106 babies were referred via the neonatal hearing screening programme to paediatric audiology. Eleven children were operated on during the coronavirus disease 2019 study period. None of the 11 children developed coronavirus symptoms. Discussion It is widely recognised that the demands of managing the current pandemic may compromise screening, clinical assessment and elective surgery. Time-sensitive issues such as cancer management have gained prominence, but a similar need exists for timely paediatric cochlear implantation. Conclusion Implantation in the paediatric population during the coronavirus disease 2019 pandemic is feasible with careful planning.
Core Ideas Personal care products and pharmaceuticals in biosolids are a concern. Concentrations in biosolids are expressed in terms of a daily reference dose. Exposure from biosolids is much lower than home exposure. It would take days to millennium to reach a daily dose of compound modeled. Municipal biosolids and composts are used on agricultural soils and in urban areas. Greater visibility has resulted in increased concerns about the presence of pharmaceuticals and personal care products (PPCPs) in these materials. Scientific studies have concluded minimal potential for human health risk. Effective communication tools can express these results to the general public. Exposure assessment modeling was used to develop non‐scientific risk communication for select PPCPs in biosolids. The equivalent of one therapeutic dose or 1 d home exposure was used. The exposure pathways included direct ingestion of biosolids, dermal absorption, drinking runoff from biosolids, and eating crops grown in biosolids. Values for biosolids‐PPCP concentrations were derived from peer‐reviewed literature and a voluntary sampling. In the highest exposure case, it would take 1.5 d for a child playing in biosolids compost to reach an equivalent to 1 d of home exposure to bisphenol A (BPA). However, concentrations of BPA were below detection (500 µg kg−1) in three of four biosolids composts sampled. For all other compounds modeled, it would take years (triclosan) to millennia (acetaminophen, fluoxetine, ibuprofen, azithromycin, ciprofloxacin, erythromycin, ofloxacin, sulfamethoxazole) of exposure to biosolids to reach the equivalent of one therapeutic dose or a 1 d home exposure.
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