title: Tissue responses to low protracted doses of high LET radiations or photons: early and late damage relevant to radio-protective countermeasures.
abstract: Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered.  Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented.  Low dose rates per fraction were used in some neutron experiments.  Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for gamma-radiation.  When total doses of 96 or 247 cGy of neutrons or gamma rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation.  During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and gamma-irradiated mice.  CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30.  Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates.  The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses.  The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis.  The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur.  In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect.  After high single doses of neutrons or gamma rays, a significant age- and radiation-related deficiency in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells.  Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for gamma rays.  The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants.  Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.
authors.affiliation: Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
authors.forename: E J
authors.initials: EJ
authors.lastname: Ainsworth
authors.forename: S M
authors.initials: SM
authors.lastname: Afzal
authors.forename: D A
authors.initials: DA
authors.lastname: Crouse
authors.forename: W R
authors.initials: WR
authors.lastname: Hanson
authors.forename: R J
authors.initials: RJ
authors.lastname: Fry
mesh_terms: D000375:Aging; D000818:Animals; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005269:Femur / Q000473:pathology / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects; D006413:Hematopoietic System / Q000473:pathology / Q000528:radiation effects*; D018499:Linear Energy Transfer; D008297:Male; D051379:Mice; D009502:Neutrons / Q000009:adverse effects; D017785:Photons / Q000009:adverse effects*; D011833:Radiation Injuries, Experimental / Q000473:pathology; D011835:Radiation Protection / Q000379:methods / Q000592:standards*; D013026:Space Flight; D013154:Spleen / Q000473:pathology / Q000528:radiation effects; D013997:Time Factors
chemical_list: D004247:DNA