Cysteamine Protection Against Irradiation Effects on Growing Cartilage

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Abstract
The therapeutic use of radiation approaches the ideal when a truly selective effect can be produced on a tumor with minimal changes in normal tissues that may be exposed to the treatment beam. This is rarely achieved and a certain amount of radiation injury invariably occurs. With elaboration of radiotherapeutic technics, including supervoltage therapy, rotational methods, and various shielding devices, physical methods of protecting tissues have achieved a place in clinical practice. The study to be reported here is the first part of a broad program of investigation of chemical methods of protecting segmentally irradiated organs and tissues as in standard radiotherapeutics. In the past decade, the study of radioprotective substances has received increasing attention not only from the radiotherapeutic point of view but also in relation to their role in threatened atomic warfare. Of particular interest in the development of current concepts of chemical radioprotection is the work of Patt (1) and associates, who took as their starting point the in vitro studies of Barron (2). These studies showed that fully crystallized enzymes or enzyme systems were much more sensitive to x-rays if they contained thiol groups and that, if an excess of cysteine were added, these enzymes could be reactivated and protected against ionizing irradiation. Patt observed that in rats the lethal effects of exposure to x-rays could be diminished by the intravenous injection of a large dose of cysteine several minutes before irradiation, thus establishing the phenomenon of protection in mammals following total-body irradiation. The impetus for this study of protection of specific tissues under conditions of localized irradiation was the findings in the long-term survivors following radiotherapy for Wilms's tumor and neuroblastoma at the University of Rochester Medical Center (see page 539 of this issue). The radiation sequelae in these survivors have included vertebral body deformity, scoliosis, and underdevelopment of portions of the pelvis as a result of injury to growing cartilage. The present research represents an attempt to construct a biologic model for the experimental solution of these problems. The sulfhydryl compound, cysteamine, was chosen as the chemical agent because there has been some indication that it localizes in cartilage. Its potency has been estimated to be five times that of cysteine in equimolecular quantities. Our aim, therefore, was to investigate the possible protection of growing cartilage from the deleterious effects of irradiation by the use of cysteamine administered intraperitoneally prior to segmental irradiation. Review of Literature A brief chronology of reports of protection against radiation effects by sulfhydryl compounds follows: