Mouse genomic associations with in vitro sensitivity to simulated space radiation.

Exposure to ionizing radiation is considered by NASA to be a major health hazard for deep space exploration missions. Ionizing radiation sensitivity is modulated by both genomic and environmental factors. Understanding their contributions is crucial for designing experiments in model organisms, evaluating the risk of deep space (i.e. high-linear energy transfer, or LET, particle) radiation exposure in astronauts, and also selecting therapeutic irradiation regimes for cancer patients. We identified single nucleotide polymorphisms in 15 strains of mice, including 10 collaborative cross model strains and 5 founder strains, associated with spontaneous and ionizing radiation-induced in vitro DNA damage quantified based on immunofluorescent tumor protein p53 binding protein (53BP1) positive nuclear foci. Statistical analysis suggested an association with pathways primarily related to cellular signaling, metabolism, tumorigenesis and nervous system damage. We observed different genomic associations in early (4 and 8 h) responses to different LET radiation, while later (24 hour) DNA damage responses showed a stronger overlap across all LETs. Furthermore, a subset of pathways was associated with spontaneous DNA damage, suggesting 53BP1 positive foci as a potential biomarker for DNA integrity in mouse models. Our results suggest several mouse strains as new models to further study the impact of ionizing radiation and validate the identified genetic loci. We also highlight the importance of future human in vitro studies to refine the association of genes and pathways with the DNA damage response to ionizing radiation and identify targets for space travel countermeasures.

Training promotores to lead virtual hereditary breast cancer education sessions for Spanish-speaking individuals of Latin American heritage in California.

BACKGROUND: Awareness about hereditary breast cancer and the preventative steps to minimize disease risk is lower in Hispanic/Latina individuals than non-Hispanic White women in the United States. For this reason, we developed a promotor-based hereditary breast cancer education and risk identification program for self-identified Hispanic/Latina women, which included training promotores in basic genetics and hereditary breast cancer. This study explored promotores' experiences receiving training and participating in virtual practice sessions as well as changes in knowledge about hereditary breast cancer. METHODS: A total of ten promotores underwent a two-week basic training led by the promotores organization and an eight-hour in person hereditary breast cancer training workshop. Demographic information along with pre- and post-training surveys were completed by ten promotores who participated in the training workshop. Surveys were given to determine changes in knowledge of hereditary breast cancer and genetics. Of the ten promotores, two were selected to lead community education sessions and participated in 6 semi-structured interviews. All interviews and practice sessions were conducted using a virtual platform. RESULTS: The data revealed that after the 8-h workshop and practice sessions, promotores felt confident about their ability to conduct virtual education sessions with the community. Interviews identified key facilitators to success such as a supportive environment, practice presentations, and personal motivation. Learning the online platform was considered the biggest challenge by the promotores, as opposed to learning complex genetics topics. CONCLUSIONS: These results provide further evidence supporting promotores' willingness and ability to provide health education on relatively complex topics. It also offers insight into the challenges of presenting information to vulnerable populations using an online platform and the additional support that is required to ensure a positive outcome.

Community research collaboration to develop a promotores-based hereditary breast cancer education program for Spanish-speaking Latinas.

Breast cancer (BC) is the most common cancer in Latinas and the leading cause of cancer death. Latinas tend to be diagnosed at later stages, receive poorer quality care and have a higher risk of mortality than non-Latina White (NLW) women. Among women with a genetic predisposition to hereditary BC, genetic counseling can be beneficial. Latinas participate in genetic counseling at lower rates than NLW women. The goal of this study was to develop comprehensive, culturally appropriate materials for community health educators (promotores)-led hereditary BC education program for Spanish-speaking Latinas. We developed the curriculum through feedback from 7 focus groups, with a total of 68 participants (35 promotores and 33 community members). We used a mixed-methods approach that relied on quantitative analysis of survey questions and qualitative content analysis of the focus groups transcripts. Pre and post promotores' training survey responses suggested improvement in the promotores' cancer-related knowledge. Themes that emerged from the qualitative analyses were (i) barriers to health education and/or care; (ii) importance of educating the Latino community about BC and genetics and (iii) role of the promotores. Future research will further evaluate the impact of the program in promotores' knowledge and community members' screening behaviors.

DNA Damage Baseline Predicts Resilience to Space Radiation and Radiotherapy.

Deep space exploration will require real-time, minimally invasive monitoring of astronaut health to mitigate the potential health impairments caused by space radiation and microgravity. Genotoxic stress in humans can be monitored by quantifying the amount of DNA double-strand breaks (DSBs) in immune cells from a simple finger prick. In a cohort of 674 healthy donors, we show that the endogenous level of DSBs increases with age and with latent cytomegalovirus infection. To map the range of human responses to space radiation, we then study DSB induction and repair in immune cells from 319 healthy donors after the cells are exposed to galactic cosmic ray components and lymphocytes from 30 cancer patients after radiotherapy. Individuals with low baseline DSB have fewer clinical complications, enhanced DNA damage repair responses, and a functional dose-dependent cytokine response in healthy donor cells. This supports the use of DSB monitoring for health resilience in space.