Detection of changes in LOH Profile of TK mutants of Human Cultured Cells (LOH)
Research Area: Cellular Biology
Expedition(s): 18
Principle Investigator(s): ● Fumio Yatagai, PhD, Institute of Physical and Chemical
Research, Wako, Japan
RESEARCH OBJECTIVES
Detection of Changes in LOH Profile of TK Mutants of Human Cultured Cells (LOH) addresses
genetic alterations in immature immune cells. LOH uses lymphoblastoid (immature immune)
cells to detect potential changes on the chromosome after exposure to cosmic radiation.
EARTH BENEFITS
The developed system for mutation (LOH) analysis is suggested to be applicable for evaluating
various cellular responses to low-dose, low-dose-rate ionizing radiation, therefore providing a
better estimation of the influence radiation exposure has on crew member health.
SPACE BENEFITS
Future crew members can benefit from the
data obtained in this investigation by
understanding the effects of radiation on
human cells and may lead to the
development of new countermeasures.
Furthermore, researchers expect to obtain
a better understanding of DNA repair
mechanisms under such condition.RESULTS
Researchers observed an increase (2.3-
fold) in thymidine kinase deficient (TK-)
mutations. Loss of heterozygosity (LOH)
analysis on the mutants also demonstrated
an increase in proportion of the large
deletion (beyond the TK locus) events,
6/41 (in-flight samples) and 1/17 (ground
control). Furthermore, in-flight samples
exhibited 48% of the ground-control level
of TK- mutation frequency upon exposure
to a subsequent 2 Gy X-rays, suggesting a
tendency of radioadaptation when
compared with the ground control
samples. The tendency of radioadaptation
was also supported by the post-flight assays on DNA double-strand break repair: a 1.8- and 1.7-
fold higher efficiency of in-flight samples compared to ground control via non-homologous end-
joining and homologous recombination, respectively. These observations suggest that this
The Monitoring of the LOH Experiment in the International
Space Station from Earth. JAXA image.