EXPERIMENTAL INDUCTION OF NEUROFIBROMATOSIS IN BICOLOR DAMSELFISH

Damselfish neurofibromatosis (DNF) is a neoplastic disease affecting t he peripheral nervous system and chromatophores of bicolor damselfish Pomacentrus partitus on Florida (USA) reefs. This report presents the results of transmission experiments using intramuscular and intraperit oneal injection of a variety of tumor preparations to induce DNF. Neur ofibromas developed within 1 yr of injection in 76% of fish injected w ith homogenates of spontaneously occurring tumors with earliest tumor development occurring at 5 to 6 wk post-injection. Cell-free transmiss ion using 0.2 mu m filtrates of DNF tumor homogenates was observed, de monstrating that the agent responsible for DNF is subcellular. Four ou t of five tumor cell lines established from neurofibromas were found t o be tumorigenic when injected, while cells cultured from normal fish had no effect, indicating that the etiologic agent of DNF was present and infectious in tumor cell lines but not in cell Lines or primary cu ltures derived from healthy fish. Serial passages of tumors were condu cted through 19 passage generations in vivo. A comparison of the cumul ative time to tumor distributions showed that most experiments beyond the third serial passage yielded significantly faster tumor developmen t than was obtained by passaging from spontaneous tumors. Induced tumo rs exhibited more localized growth patterns and were typically more ra pidly growing and more rapidly lethal than spontaneous tumors. In cont rast to the differences in growth patterns observed, the histological phenotype of the spontaneous, wild-type DNF lesions was indistinguisha ble from that of the induced tumors obtained from serial passages as w ell as in experiments involving cell-free filtrates and cultured tumor cells. These observations indicate that the process of neoplastic tra nsformation is relatively stable in this system, with Little or no phe notypic drift caused by these manipulations. Naturally occurring, tran smissible cancers that arise from cells of the central or peripheral n ervous system or from chromatophores have not been previously identifi ed. Thus, DNF is a unique disease and may provide an important model f or investigating this rather unique form of viral oncogenesis.