Accommodative responses to chronic irradiation: effects
of dose, dose rate, and pharmacological response modifiers.
Seed TM, Inal C, Dobson ME, Ghose S, Hilyard E, Tolle D, Fritz
TE.
Radiation Casualty Research Team, Armed Forces Radiobiology Research
Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA.
Low-level radiation exposures are expected to have long-term health
implications but few near-term effects that would impair function. These
assumptions are based on extrapolation from acute exposure responses, not
on studies of a larger array of exposure scenarios (e.g., protracted
exposures) that might present as operational threats. Protracted exposure
is one scenario that needs to be better defined in terms of both the
initial effect and the long-term health consequences. Reported here are
the near-term effects of chronic, low daily-dose gamma-irradiation (3-128
mGy per day) on the blood-forming system of canines. Change in
hematopoietic capacity was monitored along with time of exposure and
cumulative radiation dose. The rate, magnitude, and timing of suppression
and accommodation were determined. The ability of periodic treatment with
a lipopolysaccharide immunomodulator to alleviate the suppressive
hematopoietic effects of chronic exposure was tested. The effects of
other pharmacologics (amifostine, granulocyte colony-stimulating factor,
cytokine) are projected on the basis of current research using rodent
models. Results indicated that low but significant suppression of blood
leukocyte and platelet levels occurred at 3 mGy per day. As the dose rate
increased from 3 mGy to 128 mGy per day, the rate of suppression
increased approximately eightfold, whereas the time to accommodate
declined from 2,000 days to approximately 150 days. Within the time frame
required to reach the upper limit of 700 mGy, none of the dose rates
examined elicited blood cell decrements large enough to severely
compromise near-term immune function. Pharmacological intervention with
lipopolysaccharide minimized hematopoietic suppression in only a small
fraction of the treated animals that displayed distinctive long-term
survival and pathology patterns. Comparable short-term benefits of
treatment with hematopoietic cytokines or chemoprotectants are predicted
on the basis of responses noted in rodent models. Long-term benefits of
such treatments remain to be determined. Future work will require the
application of advanced molecular tools to more fully assess potential
pathophysiological responses and their modulation after low-level
radiation exposure.
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