EXPERIMENTAL LATHYRISM An Autoradiographic Study

In normal and lathyritic chick embryos bone collagen was synthesized primarily in the periosteum of the femurs, and was organized as radioactive spicules in these bones. Saline extraction of the lathyritic bones removed the radioactive spicules, although they eventually seemed to become non-extractable. Normal bone seemed to be unaffected by saline extraction. Marked variation in the degree of isotope incorporation was seen in collagenous and non-collagenous tissues. All the tissues of any one embryo, however, showed a similar degree of isotope incorporation. Tritiated ~-aminopropionitrile was diffusely distributed throughout bone and was completely removed by saline extraction. This autoradiographic study supports the postulate that a portion of extractable lathyritic collagen is recently synthesized and is organized in fibrous structures in bone. The pathogenesis of experimental lathyrism may involve alterations of collagen molecular structure (1), suggested by the occurrence of two abnormal properties of lathyritic collagen. Fibrils formed from lathyritic collagen, either in vivo or in vitro, are temperature sensitive, going back into solution upon cooling (2). In addition to this manifestation of altered intermolecular bonding, lathyritic collagen contains virtually no intramolecular cross-links (3, 4). A portion of lathyritic collagen seems to be newly synthesized (1, 5, 6), although Tanzer and Gross (1) have presented evidence indicating that lathyrism may also affect older collagen fibrils. Furthermore, their studies suggested that lathyritic collagen occurs as fibrils in vivo, contrary to the postulate (5, 6) of impaired fibril formation. This paper reports autoradiographic studies concerning the origin of lathyritic collagen and its morphologic state in bone. E X P E R I M E N T A L P R O C E D U R E