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Rosen, Chris J.

Publications and source records attributed to Rosen, Chris J..

6 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Screening the complex biological behavior of late lanthanides through genome-wide interactions

Abstract Despite their similar physicochemical properties, recent studies have demonstrated that lanthanides can display different biological behaviors. Hence, the lanthanide series can be divided into three parts, namely early, mid, and late lanthanides, based on their interactions with biological systems. In particular, the late lanthanides demonstrate distinct, but poorly understood biological activity. In the current study, we employed genome-wide functional screening to help understand biological effects of exposure to Yb(III) and Lu(III), which were selected as representatives of the late lanthanides. As a model organism, we used Saccharomyces cerevisiae, since it shares many biological functions with humans. Analysis of the functional screening results indicated toxicity of late lanthanides is consistent with disruption of vesicle-mediated transport, and further supported a role for calcium transport processes and mitophagy in mitigating toxicity. Unexpectedly, our analysis suggested that late lanthanides target proteins with SH3 domains, which may underlie the observed toxicity. This study provides fundamental insights into the unique biological chemistry of late lanthanides, which may help devise new avenues toward the development of decorporation strategies and bio-inspired separation processes.

Pallares, Roger M. (ORCID:0000000174238706)↗
DOE OSTI2022

Heavy-Ion-Induced Lung Tumors: Dose- & LET-Dependence

There is a limited published literature reporting dose-dependent data for in vivo tumorigenesis prevalence in different organs of various rodent models after exposure to low, single doses of charged particle beams. The goal of this study is to reduce uncertainties in estimating particle-radiation-induced risk of lung tumorigenesis for manned travel into deep space by improving our understanding of the high-LET-dependent dose-response from exposure to individual ion beams after low particle doses (0.03 - 0.80 Gy). Female CB6F1 mice were irradiated with low single doses of either oxygen, silicon, titanium, or iron ions at various energies to cover a range of dose-averaged LET values from 0.2 - 193 keV/µm, using 137Cs γ-rays as the reference radiation. Sham-treated controls were included in each individual experiment totally 398 animals across the 5 studies reported. Based on power calculations, between 40 - 156 mice were included in each of the treatment groups. Tumor prevalence at 16 months after radiation exposure was determined and compared to the age-matched, sham-treated animals. Results indicate that lung tumor prevalence is non-linear as a function of dose with suggestions of threshold doses depending on the LET of the beams. Histopathological evaluations of the tumors showed that the majority of tumors were benign bronchioloalveolar adenomas with occasional carcinomas or lymphosarcomas which may have resulted from metastases from other sites.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Multidimensional genome-wide screening in yeast provides mechanistic insights into europium toxicity

Abstract Europium is a lanthanide metal that is highly valued in optoelectronics. Even though europium is used in many commercial products, its toxicological profile has only been partially characterized, with most studies focusing on identifying lethal doses in different systems or bioaccumulation in vivo. This paper describes a genome-wide toxicogenomic study of europium in Saccharomyces cerevisiae, which shares many biological functions with humans. By using a multidimensional approach and functional and network analyses, we have identified a group of genes and proteins associated with the yeast responses to ameliorate metal toxicity, which include metal discharge paths through vesicle-mediated transport, paths to regulate biologically relevant cations, and processes to reduce metal-induced stress. Furthermore, the analyses indicated that europium promotes yeast toxicity by disrupting the function of chaperones and cochaperones, which have metal-binding sites. Several of the genes and proteins highlighted in our study have human orthologues, suggesting they may participate in europium-induced toxicity in humans. By identifying the endogenous targets of europium as well as the already existing paths that can decrease its toxicity, we can determine specific genes and proteins that may help to develop future therapeutic strategies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Genome-wide toxicogenomic study of the lanthanides sheds light on the selective toxicity mechanisms associated with critical materials

Significance The growing use of lanthanides in various industries has increased the potential for human exposure to large concentrations of these heavy metals throughout the life cycle of new technologies, requiring more detailed investigations into their toxicological properties. The eukaryote model organism Saccharomyces cerevisiae is ideal to apply functional toxicogenomics tools at the system level and probe fundamental cellular functions disrupted by rare-earth metals. A comprehensive mechanistic assay was conducted to evaluate toxicity across the entire lanthanide series and provide information about which toxicological mechanisms may be shared by the different metals. We identified distinct characteristic behaviors between early and middle/late lanthanides, highlighting the powerful discrimination capabilities of natural systems and pointing to detailed mechanistic pathways associated with lanthanide exposure.

59 BASIC BIOLOGICAL SCIENCES↗