Ls PRIM IE Eatin A Araneae & Gahwed , INZURY! ITS PATHOGENESIS AND THERAPY two BRADINELON 2 stitution of elements that are no longer bein produced. Tn the second pategory, one can diatehe the mechanisin as being due to the stinmation of precursor cells that are injured, but stl capable of responding to physic logical stimul (erythropoietin, leukocytosis promoting factor, ete. that are known to exist, although not yet adequately characterized. Titerest has centered mainly around the mecharisin of the restorative effect in the first category, aud this will be pursued in some detail here (for reviews of this subject, see Cronkite and Bond; Bond and Cronkite; Jacobson; Report of U. N. Scientifie Comimittee; Pissuc Homotransplantation Confer ence). Studies on measures to induce accelerated restoration of tissues had their genesis in shielding experiments. Restoration or regeneration of most tissues occurs in the absenee of special measures if the radiation dose is low enough to allow spontancous survival (Gt is possible to have permanent atrophy of some tissues that are not essential to life, e.g., reproductive cells, or of portions of tissues that are essential to life). Of most importance for hnmediate survival at radiation doses in the lethal range is restoration of the hematopoietic tissues, and the degree to which shielding or allied procedures accelerates restoration of other tissues, or influences ultimate longevity, genetic damage or tumor induction, is not well defined. Shielding or parabiosis apparently does not protect against most types of radiation-induced neoplasms (Maisin; Brecheret al.; CourtBrown; Finerty), but does against Ivmphoma induction (Kaplan) or myelocytic leukemia (Uptonef al.) in mice. Early studies on shielding and restoration of irradiated tissues go back to Chiari (1912) and Fabricius-Méller (1921) (see Cronkite and Brecher). The later studies of Jacobson and his associates led to the concept that “humoral factors’? were present in the shielded spleen of the irradiated mouse which induced rapid restoration of the irradiated hemopoietic tis- sues elsewhere in the body. Their work and concepts are summarized in reviews by Jacobson et al. Studies on the mechanism of the protection afforded by parabiosis have been pursued by Finerty ef al., Schneider et a@l., Binhaminer ef al., and Metz et al., and it was concluded that the effect was not mediated through spleen, adrenals, or hypophysis (Finertyef al., Schneideret al.). Swift et al. successively irradiated portions of the body, followed after varying time intervals with irradiation of the entire remaining portion of the body. This procedure significantly increased the survival rate. These studies indicated strongly that the protective factor circulates and can be quickly picked up by tissues that have beenirradiated. Cole and associates have investigated the possible existence and sub- 20 | Pm cellular location of the protective “spleen factor.” Early in their work, ub 3 ch