Genetic variation and radiation quality impact cancer promoting cellular phenotypes in response to HZE exposure
| Autor: | Janice M. Pluth, Chris Wang, Shiena Enerio, Mark A. LaBarge, Deepa M. Sridharan, Martha R. Stampfer |
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| Rok vydání: | 2019 |
| Předmět: |
Genome instability
010504 meteorology & atmospheric sciences Health Toxicology and Mutagenesis Pilot Projects DNA damage response 01 natural sciences Cancer risk 2.1 Biological and endogenous factors Breast Aetiology 010303 astronomy & astrophysics Cells Cultured Cancer Genetics education.field_of_study HZE exposure Radiation Cultured Ecology BRCA1 Protein Agricultural and Biological Sciences (miscellaneous) Phenotype Female Genomic instability DNA repair Cells Population Breast Neoplasms Biology Centrosome aberrations 0103 physical sciences Genetic variation medicine Humans education 0105 earth and related environmental sciences Chromosome Aberrations BRCA2 Protein Human Genome Wild type Genetic Variation P16 Astronomy and Astrophysics Heterozygote advantage medicine.disease Phosphoproteins BRCA1 BRCA2 ATM Cosmic Radiation DNA Damage |
| Zdroj: | Sridharan, DM; Enerio, S; Wang, C; LaBarge, MA; Stampfer, MR; & Pluth, JM. (2019). Genetic variation and radiation quality impact cancer promoting cellular phenotypes in response to HZE exposure. Life Sciences in Space Research, 20, 101-112. doi: 10.1016/j.lssr.2018.10.002. Lawrence Berkeley National Laboratory: Retrieved from: http://www.escholarship.org/uc/item/5gb776b6 |
| Popis: | © 2018 The Committee on Space Research (COSPAR) There exists a wide degree of genetic variation within the normal human population which includes disease free individuals with heterozygote defects in major DNA repair genes. A lack of understanding of how this genetic variation impacts cellular phenotypes that inform cancer risk post heavy ion exposure poses a major limitation in developing personalized cancer risk assessment astronauts. We initiated a pilot study with Human Mammary Epithelial Cell strains (HMEC) derived from wild type, a p16 silenced derivative of wild type, and various genetic variants that were heterozygote for DNA repair genes; BRCA1, BRCA2 and ATM. Cells strains were exposed to different high and low LET radiation qualities to generate both simple and complex lesions and centrosome aberrations were examined as a surrogate marker of genomic instability and cancer susceptibility post different exposures. Our results indicate that centrosome aberration frequency is higher in the genetic variants under study. The aberration frequency increases with dose, complexity of the lesion generated by different radiation qualities and age of the individual. This increase in genomic instability correlates with elevated check-point activation post radiation exposure. These studies suggest that the influence of individual genetics on cell cycle regulation could modify the degree of early genomic instability in response to complex lesions and potentially define cancer predisposition in response to HZE exposure. These results will have significant implications in estimating cancer susceptibility in genetically variant individuals exposed to HZE particles. |
| Databáze: | OpenAIRE |
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