Radiation sickness has up to now been considered exclusively a complication in radiation exposure to a relatively large area such as whole body radiation, exposure to abdomen etx. Recently this syndrome has attracted more general interest as an important effect of routine exposures to irradiation. The problem of treating radiation sickness has consequently become one of great timeliness and importance.
The fundamental causes and mechanism of irradiation sickness are not known and therefore methods of treatment thus far proposed have met with little significant success, although irradiation sickness has harrassed hpysicians and patients alike
since roentgen rays and radium were first utilized as therapeutic agents.
The wide variety of etiologic factors elicited from reviews of the literature attest to the lack of fundamental knowledge of this condition.
To correlate other alleged etiologic mechanisms of irradiation sickness and arrive at a single causative agent is perhaps impossible.
Ellinger stated that radiation sickness represents a symptom complex involving numerous systems of the body.
Symptomatology of radiation sickness points to adrenal cortical insufficiency. Radiation sickness thus represents a typical case of "adaptation syndrome" of Seyle, the non-specific respones of the body to stress, irrespective of its causation by chemicals, bacterial toxins, or physical agents. He described mechanism of radiation sickness as follow; Irradiation of sufficiently large volume of the body results in the release of or photochemical production of histamine-like substances, if not of histamine itself. These substances cause the anterior pituitary to secrete corticotropic hormone, which in turn stimulates adrenal cortical activity. This stimulation may well result in exhaustion of the gland. Thus the histamine or histamine-like substances are demonstrated to have an important role in systemic and local radiation syndromes.
Irradiation was stated to cause decrease in number as well as degranulation and disruption of mast cells whereas other whereas other reported the contrary.
It has been claimed that tissue mast cells produce the histamine in close relation with capillary permeability and production of histamine and that mast cells also produce heparin, hyaluronic acid and 5-hydroxytryptamine (serotonin).
There have been conflicting reports on the relationship between cortisone, ACTH and radiation syndrome, local and general. Some consider cortisone to be effective for the radiation syndrome whereas other deny favorable any effect of cortisone for this.
On the other hand, it was pointed out that adrenal cortical hormone has an antihistaminic effect by inactivating histamine.
There also has been a large body of controversy concerning the effect of antihistamine on radiation sickness. Benefical effects against the "radiation syndrome" were obtained with antihistamine. The benefical effects of antihistamine on allergic and histamine effects are thought to be due to antihistamine acting as a competitive activator against histamine in relation to its receptor, although some doubt about this mechanism.
Large doses of antihistamine, on the contrary, acted as a precipiating factor in reducing survival time and caused increased destruction or disruption of mast cells in animals after irradiation.
All these controversial reports and uncertainties regarding the effects of radiation on mast cells and the relationship of cortisone and antihistamine to them, has provided the impetus for this investigation.
Materials and methods
227 adult albino rats of both sexes weighing over 200 gms. each, were arranged in six groups: 1) Control group, 2) Radiation control group, 3) Cortisone group, 4) Radiation with cortisone group, 5) Antihistamine group and 6) Radiation with antihistamine group.
The rats were slaughtered on the following schedule: 1) Immediately after irradiation(O hours), 2) 3 hours, 3) 6 hours 4) 12 hours, 5) 24 hours, 6) 2 days, 7) 3 days, 8) 5 days, 9) 7 days, 10) 11 days and 11) 15 days post irradiation. Antihistamine 10 mg. or cortisone 5 mg. when administered, was given intramuscularly one hour before irradiation.
The mesenteries of the rats excised, fixed and stained with toluidin blue or Wright's or Pough's method for examinations of the metachromatic changes in the tissue mast cells.
A count of 100 mesenteric mast cells were made under 400x magnification.
The degrees of degranulation and disruption of mast cells were arbitrarily divided into four types: 1) Intact or normal, 2) Grade 1 : slight degranulation, 3) Grade 11: moderate degranulation, and 4) Grade 111: marked or severe degree of
degranulation and disruption.
Radiaton factors were employed as follows: An 800r whole body radiation dose was administered from above the rat with 250kvp Grneral Electric Therapeutic Units. The technical factors were: 220kvp, 15Ma, Focus-Object Distance 50cm., using Thoraeus filter 11(0.4mm Sn., 0.25mm Cu. and 1mmA1.) r/min, measured on the air 25r. The X-ray unit was calibrated before and after each experiment with a Victoreen r-chamber.
The experimental results may be summarized as follows:
1) In the whole body radiation group: There was a significant
decrease(83.3%±5.2) in the number of normal and intact mast cells with concommitant increase in the abnormal and atypical mast cells of the mesentery at 6 hours after irradiation and reaching a macimum decrease (64.0%±5.3) of normal mast cells 24 hours after irradiation. At 2 days post irradiation normal mast cells showed an increase, returning to almost normal (97.0%±2.7) 15 days after irradiation. These findings seem to indicate that irradiation has destructive action on mast cells of the mesentery, causing degranulation and disruption, with resultant increase in the number of atypical and abnormal mast cells.
2) In cortisone treated group: There also was noted an acute decrease of normal mast cells (87.6%±2.5) accompained by increased abnormal and atypical mast cells beginning immediately after administration of cortisone and reaching a maximum decrease(63.3%±2.8) in 12 hours, with an increase of normal status around 15 days. These findings indicate that cortisone also has disruptive and degranulating effects on mast cells causing increase in the number of atypical and abnormal cells associated with decrease in the normal and intact mast cells.
3) In irradiation and cortisone treated group: No significant decrease of normal and intact mast cells count was noted in the mesentery at 6 to 24 hours after irradiation, in contrast to the marked decrease of normal mast cells in the irradiation group alone and in the cortisone treated group alone. All these findings suggest that cortisone given prior to irradiation acts as a protective or inhibitory factor against the disruptive effects of radiation on the mesenteric mast cells.
4) In antihistamine treated group: There was noted a decrtease of normal and intact mast cells (78.3%±2.9) accompanied by increased number of degranulated and disrupted atypical mast cells in the mesentery, occurring immediately after administration of antihistamine and reaching a maximum decrease (70.0%±0) at 12 hours after its administration, but gradually returning to normal status starting 2 days after administration of antihistamine. These findings suggest that antihistamine also causes degranulation and destruction of mast cells of the mesentery which may be closely correlated with the "histamine releasing" effects of antihistamine.
5) In the irradiation and antihistamine treated group: One noted no significant decrease of normal mast cell count of the mesentery 6 to 24 hours in contrast to the groups treated by radiation or antihistamine alone.
These findings indicate that administration of antihistamine prior to irradiation acted as an inhibitory and protective agent on the degranulating and destructive effects of radiation to the mast cells of the mesentery.
6) Survival rate of animals: There was no mortality among the experimental groups in this series except in the "irradiation alone" group where the mortality was 17(24.3%) out of 70 animals.
This strongly suggests the beneficial and protective effects of cortisone and antihistamine on survival time of rats following whole body irradiation.
In the experiments herein summarized, whole body irradiation, administration of cortisone or antihistamine alone can give rise to degranulation and disruption of mast cells accompanied by increased number of abnormal and atypical mast cells of the mesentery.
Administration of cortisone or antihistamine prior to whole body irradiation caused marked inhibition of and protection to similar degree against degranulating and destructive actions of whole body irradiation, suggesting that cortisone and antihistamine may be beneficial as a prophylactic against radiation sickness.