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Office
of Biological and Environmental Research
DOE
Lowdose Radiation Program Workshop IV
2003
Abstract
Title:
The Role of Flavin Containing Oxidases in the Response of Normal
Human Diploid Fibroblasts to Low Dose/Very Low Dose Rate y-radiation
Authors:
Perumal Venkatachalam†, Sonia M. de Toledo†,
Roger W. Howell†, Douglas R. Spitz* and Edouard
I. Azzam†
Institutions:
†Department
of Radiology, UMDNJ – New Jersey Medical School, Newark,
NJ
*Free
Radical and Radiation Biology Program, Department of Radiation
Oncology, University of Iowa, Iowa City, IA
To investigate
the contribution of oxidative metabolism from cell membrane
originating pathways to the cellular response to low dose/low
LET radiation, we have examined the effects of flavin containing
oxidase enzymes on the level of residual DNA damage in normal
human diploid fibroblasts exposed to 10 cGy from y-rays
delivered over 24 or 48 hours. Our preliminary data indicate
that such oxidases significantly contribute to the cellular
response at low dose exposure. Interestingly, perturbation
of the cellular redox state by inhibiting these oxidases with
diphenyl iodonium induces a G1 checkpoint and results
in highly significant perturbations in the expression levels
of key cell cycle regulatory proteins (e.g. p21wafl
and cyclin D1) and of p38mapk in control non-irradiated
quiescent cells. These data emphasize the critical role of
endogenous oxidative metabolism in modulating the cellular
response to low dose ionizing radiation. They are consistent
with previous observations (Narayanan et. al., 1997,
Azzam et al., 2002) that NAD(P)H-ozidases modulate
the expression of stress effects in bystander cells present
in the vicinity of irradiated cells.
Supported
by Research Grand FG02-02ER63447 from the U.S. Department
of Energy.
