Search

New molecular cytogenetic biomarkers may significantly contribute to biodosimetry, whose application is still globally diverse and not fully standardized. In 2011, a new term, chromothripsis, was introduced raising great interest among researchers and soon motivating further investigations of the phenomenon. Chromothripsis is described as a single event in which one or more chromosomes go through severe DNA damage very much resembling rogue cells (RC) described more than 50 years ago. In this review, we for the first time compare these two multi-aberrant cells types, RC versus chromothriptic cells, giving insight into the similarities of the mechanisms involved in their etiology. In order to make a better comparison, data on RC in 3366 subjects from studies on cancer patients, Chernobyl liquidators, child victims of the Chernobyl nuclear plant accident, residentially and occupationally exposed population have been summarized for the first time. Results of experimental and epidemiological analysis show that chromothriptic cells and RC may be caused by exposure to high LET ionizing radiation. Experience and knowledge collected on RC may be used in future for further investigations of chromothripsis, introducing a new class of cells which include both chromothriptic and RC, and better insight into the frequency of chromothriptic cell per subject, which is currently absent. Both cell types are relevant in investigations of cancer etiology, biomonitoring of accidentally exposed population to ionizing radiation and biomonitoring of astronauts due to their exposure to high LET ionizing radiation during interplanetary voyages.

The development of systems that are more accurate and time-efficient in predicting safety and efficacy of target products in humans are critically important in reducing the cost and duration of pharmaceutical development. To circumvent some of the limitations imposed by the use of animal models, ex vivo systems, such as precision-cut lung slices (PCLS), have been proposed as an alternative for evaluating safety, immunogenicity and efficacy of vaccines and pharmaceuticals. In this study, we have established a human PCLS system and methodology for PCLS cultivation that can provide long-term viability and functionality in culture. Using these techniques, we found that cultured PCLS remained viable for at least 14 d in culture and maintained normal metabolic activity, tissue homeostasis and structural integrity. To investigate whether cultured PCLS remained functional, lipopolysaccharide (LPS) was used as a target stimulating compound. We observed that after an 18-hour incubation with LPS, cultured PCLS produced a set of pro-inflammatory cytokines, including TNF-alpha, IL-1 beta, IL-6 and IL-10 as well as the enzyme COX-2. Furthermore, cultured PCLS were shown to be capable of generating re-call immune responses, characterized by cytokine production, against antigens commonly found in routine vaccinations against influenza virus and tetanus toxoid. Taken together, these results suggest that human PCLS have the potential to be used as an alternative, high-throughput, ex vivo system for evaluating the safety, and potentially immunogenicity, of vaccines and pharmaceuticals.

Cells with specific multiple chromosome aberrations, defined as rogue cells (RC) have been described in different populations, predominantly those exposed to radiation. The frequency, etiology and related health risks have still not been elucidated due to their low frequency of occurrences and rarely performed studies. This study reports RC frequency using chromosome aberration (CA) assay in peripheral lymphocytes in the group of 3242 subjects, during a 30-year long follow-up study in a general rural and urban population, children environmentally exposed to radon, occupationally exposed population and lung cancer patients from the Kemerovo region (Siberia, Russian Federation). Results show that the highest RC frequency was present in children environmentally exposed to radon and the lowest in the general urban population. Total frequency of CA did not correlate with frequency of RC. Genotoxic analysis of air and water samples excluded anthropogenic pollution as a possible cause of genome damage and RC frequency. In 85% of RCs, double minutes, observed in a large number of human tumors, were present. Results of CA analysis suggested that radon and its decay products (alpha-emitters) were the leading factors causing RC in subjects exposed to high LET radiation. Thus, RC may be a candidate biomarker for exposure to this type of radiation.