Blood responses under chronic low daily dose gamma irradiation: II. Differential preclinical responses of irradiated female dogs in progression to either aplastic anemia or myeloproliferative disease

Abstract

Female beagle dogs were chronically exposed to low daily doses of 60Co gamma rays (7.5 cGy day −1) and responded in one of three distinct hemopathological patterns. These patterns, reflective of distinct subgroups, were characterized by (a) low radioresistance resulting in progressive hematopoietic suppression, terminal aplastic anemia (AA), and relatively short (<400 days) survival ( −S-AA subgroup); (b) high radioresistance, initially coupled with strong but aberrant regenerative hematopoiesis, and later with the development of myeloproliferative disease (MPD) ( +-R-MPD subgroup); and (c) high radioresistance, coupled with an early phase of strong regenerative hematopoiesis, but later with no myeloproliferative disease ( +R-nonMPD subgroup). In this study, the changes in circulating blood cell levels (granulocytes, monocytes, erythrocytes, lymphocytes and platelets) were sequentially assessed in time and fitted to a flexible, quadratic-linear-type response model previously developed. These analyses provided definition to (a) an initial suppressive, radiotoxic phase and (b) the subsequent recovery phase for each of these subgroups. The magnitude and severity of blood cell loss during the initial suppressive phase was generally greatest in the −S-AA subgroup and lowest in the +R-nonMPD subgroup, with the +R-MPD subgroup showing intermediate level responses. A notable exception included a very high net loss of blood granulocytes by the +R-nonMPD subgroup relative to the other two subgroups. By contrast, the magnitude of blood cell restoration, as well as blood cell maintenance levels during the secondary, recovery phase, was generally highest in the +R-MPD subgroup, of intermediate strength in the +R-nonMPD subgroup, and extremely weak or absent in the −S-AA subgroup. Notable exceptions were in the +R-nonMPD subgroup's high recovery rates of monocyte and lymphocyte blood levels, as well as the high maintenance levels of blood granulocytes during recovery. These results are consistent with our earlier observations of blood responses of chronically irradiated male dogs, in that subgroups of female dogs prone to specific radiogenic hematopathologies (i.e. AA and MPD) can be readily identified and staged in specific preclinical periods by a series of marked differential blood responses.