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Title: Genetic variation and radiation quality impact cancer promoting cellular phenotypes in response to HZE exposure

Journal Article · · Life Sciences in Space Research
 [1];  [1];  [1]; ORCiD logo [2];  [1];  [3]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. City of Hope National Medical Center, Duarte, CA (United States)
  3. Univ. of Nevada, Las Vegas, NV (United States)
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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.

Research Organization:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1542365
Journal Information:
Life Sciences in Space Research, Vol. 20, Issue C; ISSN 2214-5524
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 3 works
Citation information provided by
Web of Science

Figures / Tables (8)

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.