The molecular mechanisms underlying radiation-induced defects in the b
one marrow which may contribute to the development of radiation-induce
d hematopoietic disorders such as aplastic anemia and leukemia are not
known. Persistent changes in gene expression were examined after expo
sure of cells of a murine bone marrow stromal cell line to ionizing ra
diation, Analysis of mRNA transcript levels by differential display le
d to the identification of a band, C122, which increased in abundance
1 week after exposure. Northern blot hybridization verified these resu
lts and revealed a 12-fold increase in abundance of this message for u
p to 3 weeks after irradiation in vitro. DNA sequence analysis identif
ied clone C122 as murine serum amyloid A 3 (Saa3), a member of the Saa
family of acute-phase or inflammatory response genes. Saa message lev
els were then examined in vivo in the bone marrow of mice exposed to t
otal-body irradiation. Semi-quantitative reverse transcription-polymer
ase chain reaction revealed a 15-20-fold increase in Saa3 message leve
ls in the bone marrow of irradiated mice from 3 days to 2 weeks after
exposure. Saa3 message levels continued to be 2-3-fold above control f
or up to 28 weeks in vivo. Two additional members of the murine Saa ge
ne family, Saa1 and Saa2, were also detected in irradiated bone marrow
. The expression of SAA1 and SAA2 was also detected in irradiated cell
s of human bone marrow stromal cell lines in vitro. These results sugg
est that SAA genes are involved in the radiation response in the bone
marrow, but their role in the recovery of the marrow after irradiation
or in the development of radiation-induced hematopoietic disorders re
mains to be established. Additionally, the persistent radiation-induce
d increase in expression suggests the potential utility of using SAA3
transcript levels as a molecular marker of past radiation exposure. (C
) 1998 by Radiation Research Society.