Children are at a greater risk than adults of developing cancer after being exposed to ionizing radiation. Because of their developing bodies and long life expectancy post-exposure, children require specific attention in the aftermath of nuclear accidents and when radiation is used for diagnosis or treatment purposes. In this review, we discuss the carcinogenic potential of pediatric exposures to ionizing radiation from accidental, diagnostic, and therapeutic modalities. Particular emphasis is given to leukemia and thyroid cancers as consequences of accidental exposures. We further discuss the evidence of cancers that arise as a result of radiotherapy and conclude the review with a summary on the available literature on the links between computer tomography (CT) and carcinogenesis. Appropriate actions taken to mitigate or minimize the negative health effects of pediatric exposures to ionizing radiation and future considerations are discussed.

The goal of this study was to investigate Cannabidiol (CBD) hepatotoxicity in 8-week-old male B6C3F₁ mice. Animals were gavaged with either 0, 246, 738, or 2460 mg/kg of CBD (acute toxicity, 24 h) or with daily doses of 0, 61.5, 184.5, or 615 mg/kg for 10 days (sub-acute toxicity). These doses were the allometrically scaled mouse equivalent doses (MED) of the maximum recommended human maintenance dose of CBD in EPIDIOLEX^® (20 mg/kg). In the acute study, significant increases in liver-to-body weight (LBW) ratios, plasma ALT, AST, and total bilirubin were observed for the 2460 mg/kg dose. In the sub-acute study, 75% of mice gavaged with 615 mg/kg developed a moribund condition between days three and four. As in the acute phase, 615 mg/kg CBD increased LBW ratios, ALT, AST, and total bilirubin. Hepatotoxicity gene expression arrays revealed that CBD differentially regulated more than 50 genes, many of which were linked to oxidative stress responses, lipid metabolism pathways and drug metabolizing enzymes. In conclusion, CBD exhibited clear signs of hepatotoxicity, possibly of a cholestatic nature. The involvement of numerous pathways associated with lipid and xenobiotic metabolism raises serious concerns about potential drug interactions as well as the safety of CBD.

Purpose: Ionizing radiation (IR) is a ubiquitous environmental stressor with genotoxic and epigenotoxic capabilities. Terrestrial IR, predominantly a low-linear energy transfer (LET) radiation, is being widely utilized in medicine, as well as in multiple industrial applications. Additionally, an interest in understanding the effects of high-LET irradiation is emerging due to the potential of exposure during space missions and the growing utilization of high-LET radiation in medicine. Conclusions: In this review, we summarize the current knowledge of the effects of IR on DNA methylation, a key epigenetic mechanism regulating the expression of genetic information. We discuss global, repetitive elements and gene-specific DNA methylation in light of exposure to high and low doses of high- or low-LET IR, fractionated IR exposure, and bystander effects. Finally, we describe the mechanisms of IR-induced alterations to DNA methylation and discuss ways in which that understanding can be applied clinically, including utilization of DNA methylation as a predictor of response to radiotherapy and in the manipulation of DNA methylation patterns for tumor radiosensitization.

Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs.

Much evidence has documented that microRNAs (miRNAs) play an important role in the modulation of interindividual variability in the production of drug metabolizing enzymes and transporters (DMETs) ...