Abstract
ABSTRACT
Charged particles like iron‐56 ions impose health risks in long‐term manned space exploration. This study was designed to define the impact of
Trp53
status upon the manifestation of mutations in the
hypoxanthine‐guanine phosphoribosyltransferase
(
Hprt
) gene in splenic T‐cells following exposure of
Trp53
wild‐type, hemizygous, and nullizygous
lacZ
transgenic mice to 1 Gy
56
Fe particles. In male and female mice necropsied at 2, 4, and 8 weeks postexposure,
Hprt
mutant frequencies in splenic T‐cells (measured via the
Hprt
mutation cloning assay) increased significantly over time to peak at 4 weeks postexposure before decreasing to lower but still elevated levels. Mutagenic potency estimates based upon the change in mutant frequency over time in exposed versus respective control groups showed that the total mutagenic response depended upon the
Trp53
genetic status, with the mutagenic burden of 1 Gy being threefold and 5.3‐fold greater in
Trp53
+/−
and
Trp53
−/−
mice, respectively, compared to
Trp53
+/+
mice.