Cancer is the second leading cause of mortality worldwide accounting for almost 10 million deaths in 2020. Current standard of care treatment varies depending on the type and stage of disease, but commonly includes surgery, chemotherapy, and/or radiation therapy. There is evidence that whole- and half-body exposure to low dose ionizing radiation can also be an effective therapeutic due to its stimulation of anti-cancer immunity. One of the limiting factors for past clinical trials using low dose radiation therapy has been adverse hematological events. However, similar hematological changes are also frequently reported following standard of care treatments in oncology. This review summarizes the effects of various cancer therapies on hematologic toxicity through the evaluation of complete blood count reports. The reviewed literature elucidates hematological trends in patients undergoing chemotherapy, and both high and low dose radiation therapy. In general, high dose radiation and chemotherapy can result in widespread changes in blood counts, with the most severe effects related to leukopenia. Overall, compared to standard of care treatments, low dose radiation results in similar, yet more mild hematological changes. Taken together, hematological toxicities should not be a limiting factor in the applicability of low dose radiation as a cancer therapeutic.

Radiation therapy for abdominopelvic malignancies often results in damage to the gastrointestinal tract (GIT) and permanent changes in bowel function. An overlooked component of the pathophysiology of radiation-induced bowel injury is the role of the gut microbiome. The goal of this research was to identify the impacts of acute radiation exposure on the GIT and gut microbiome. C57BL/6 mice exposed to whole-body X-rays (0.1–3 Gy) were assessed for histological and microbiome changes 48 h post-radiation exposure. Within the ileum, a dose of 3 Gy significantly decreased crypt depth as well as the number of goblet cells, but increased overall goblet cell size. Overall, radiation altered the microbial distribution within each of the main phyla in a dose- and tissue-dependent manner. Within the Firmicutes phylum, high dose irradiation resulted in significant alterations in bacteria from the class Bacilli within the small bowels, and from the class Clostridia in the large bowels. The 3 Gy radiation also significantly increased the abundance of bacterial families from the Bacteroidetes phylum in the colon and feces. Overall, we identified various alterations in microbiome composition following acute radiation exposure, which could potentially lead to novel biomarkers for tracking patient toxicities or could be used as targets for mitigation strategies against radiation damage.

FRA1 (FOSL1) is a transcription factor and a member of the activator protein-1 superfamily. FRA1 is expressed in most tissues at low levels, and its expression is robustly induced in response to extracellular signals, leading to downstream cellular processes. However, abnormal FRA1 overexpression has been reported in various pathological states, including tumor progression and inflammation. To date, the molecular effects of FRA1 overexpression are still not understood. Therefore, the aim of this study was to investigate the transcriptional and functional effects of FRA1 overexpression using the CGL1 human hybrid cell line. FRA1-overexpressing CGL1 cells were generated using stably integrated CRISPR-mediated transcriptional activation, resulting in a 2–3 fold increase in FRA1 mRNA and protein levels. RNA-sequencing identified 298 differentially expressed genes with FRA1 overexpression. Gene ontology analysis showed numerous molecular networks enriched with FRA1 overexpression, including transcription-factor binding, regulation of the extracellular matrix and adhesion, and a variety of signaling processes, including protein kinase activity and chemokine signaling. In addition, cell functional assays demonstrated reduced cell adherence to fibronectin and collagen with FRA1 overexpression and altered cell cycle progression. Taken together, this study unravels the transcriptional response mediated by FRA1 overexpression and establishes the role of FRA1 in adhesion and cell cycle progression.

The lens of the eye is one of the most radiosensitive tissues. Although the exact mechanism of radiation-induced cataract development remains unknown, altered proliferation, migration, and adhesion have been proposed as factors. Lens epithelial cells were exposed to X-rays (0.1–2 Gy) and radiation effects were examined after 12 h and 7 day. Proliferation was quantified using an MTT assay, migration was measured using a Boyden chamber and wound-healing assay, and adhesion was assessed on three extracellular matrices. Transcriptional changes were also examined using RT-qPCR for a panel of genes related to these processes. In general, a nonlinear radiation response was observed, with the greatest effects occurring at a dose of 0.25 Gy. At this dose, a reduction in proliferation occurred 12 h post irradiation (82.06 ± 2.66%), followed by an increase at 7 day (116.16 ± 3.64%). Cell migration was increased at 0.25 Gy, with rates 121.66 ± 6.49% and 232.78 ± 22.22% greater than controls at 12 h and 7 day respectively. Cell adhesion was consistently reduced above doses of 0.25 Gy. Transcriptional alterations were identified at these same doses in multiple genes related to proliferation, migration, and adhesion. Overall, this research began to elucidate the functional changes that occur in lens cells following radiation exposure, thereby providing a better mechanistic understanding of radiation-induced cataract development.

Lake whitefish (Coregonus clupeaformis) embryos incubated at low temperatures have a longer incubation period and hatch at a significantly greater size than those incubated at warmer temperatures. We examined hatch timing and morphological characteristics for whitefish embryos reared under different constant and varying temperatures to determine whether the thermal dependence of hatching size reflects differences in their development stage. Our results show that lake whitefish embryos hatch at different temperature-dependent developmental stages, and this is the dominant factor affecting size-at-hatch. The term “heterograde” is proposed for the thermal dependence of hatching stage to differentiate it from hatching that occurs at a fixed developmental stage. A method to quantify this effect is given using a ratio that describes the difference in relative development at hatching between different viable constant incubation temperatures. Heterograde hatching is proposed as a possible mechanism to synchronize the timing of hatch to the break-up of winter ice cover despite variability in the date of spawning and in the onset of spring break-up.

This manuscript evaluates the role of cell killing, tissue disorganization, and tissue damage on the induction of lung cancer following low dose rate radiation exposures from internally deposited radioactive materials. Beagle dogs were exposed by inhalation to ⁹⁰Y, ⁹¹Y, ¹⁴⁴Ce, or ⁹⁰Sr in fused clay particles. Dogs lived out their life span with complete pathology conducted at the time of death. The radiation dose per cell turnover was characterized and related to the cause of death for each animal. Large doses per cell turnover resulted in acute death from lung damage with extensive cell killing, tissue disorganization, chronic inflammatory disease, fibrosis, and pneumonitis. Dogs with lower doses per cell turnover developed a very high frequency of lung cancer. As the dose per cell turnover was further decreased, no marked tissue damage and no significant change in either life span or lung cancer frequency was observed. Radiation induced tissue damage and chronic inflammatory disease results in high cancer frequencies in the lung. At doses where a high frequency of chromosome damage and mutations would be predicted to occur there was no decrease in life span or increase in lung cancer. Such research suggests that cell killing and tissue damage and the physiological responses to that damage are important mechanisms in radiation induced lung cancer.