Comparative studies on the ultrastructure of malignant melanoma in fish and human by freeze-etching and transmission electron microscopy.

Malignant melanomas (MM) in the fish Xiphophorus and in humans were studied both by transmission electron microscopy (TEM) and freeze-etching (FE). In both fish and human melanomas the cells show interdigitations of the plasma membranes. The nuclei are large and lobulated and have many nuclear pores. Melanosomes are abundant and melanosome complexes ("compound melanosomes") occur regularly. Pinocytotic vesicles could be demonstrated in fish and human melanomas showing local differences in frequency and distribution patterns in the tumor. Intercellular junctions are lacking in MM cells from fish and humans. The FE technique showed considerable advantages in demonstrating membrane-surface peculiarities such as nuclear pores or pinocytotic vesicles. The FE replicas of fish melanomas are like those of humans. These findings may support the hypothesis that melanoma in fish and humans reflect the same biological phenomenon.

Cytogenetics of neoplasia of Xiphophorus.

Certain laboratory hybrid Xiphophorus fish develop heritable neoplasia. Neoplasia can also be induced in some hybrids by treatment with carcinogens. In either case the neoplasms are mediated by a "'tumor gene," that is normally controlled by linked or nonlinked "regulating genes" or both. Light and electron microscopic studies on these two types of tumors reveal important differences. The heritable tumor is a compact mass of tissue formed of densely packed melanized melanocytes often with nuclear pockets and projections. A large number of cells undergoing a process of nuclear fragmentation has been observed. The induced tumors, on the other hand, contain fewer melanized melanocytes and show a comparative increase in the amount of connective tissue. The nuclear pockets and projections commonly found in the melanocytes of the heritable tumors are not present in the melanocytes of the induced melanoma. The most important difference observed was the presence of different types of structural chromosome aberrations in the induced tumor and a total absence in the heritable ones. These anomalies seem to be epiphenomenal, and the real genetic change is subchromosomal.

Virus-like particles induced by bromodeoxyuridine in melanoma and neuroblastoma of Xiphophorus.

5-Bromodeoxyuridine (BrdUrd) injected into the muscular tissue of fish bearing melanoma or neuroblastoma induces the production of virus-like particles in these tumors. The particles in the melanoma are morphologically similar to papovaviruses of polyoma-type, those in the neuroblastoma resemble oncornaviruses of B- and C-type.

Genetic basis of susceptibility for development of neoplasms following treatment with N-methyl-N-nitrosourea (MNU) or x-rays in the platyfish/swordtail system.

Specific genotypes of the xiphophorine fish develop neoplasms following treatment with N-methyl-N-nitrosourea or X-rays. Several of these neoplasms can be related to the presence of specific chromosomes. The implication of these findings are discussed.

Genetics of susceptibility in the platyfish/swordtail tumor system to develop fibrosarcoma and rhabdomyosarcoma following treatment with N-methyl-N-nitrosourea (MNU).

About 7000 animals of 65 different genotypes of the xiphophorine fish were treated with the direct acting chemical carcinogen N-methyl-N-nitrosourea (MNU; 10(-3)M; four times for 1 hour in two week intervals), in order to find out whether the susceptibility for development of fibrosarcomas and rhabdomyosarcomas is directly related to the genotype. A genotype specific susceptibility was found, ranging from zero to about nine percent. The highest susceptibles were found in certain backcross hybrids involving P.variatus/X.helleri-hybrids and X.helleri, as the recurrent parent. These genotypes were further analysed. Both P.variatus and X.helleri, as werr as their F1 proved to be insusceptible; while from the three backcrosses, which were tested, namely the BC1, BC4 and BC15, both the BC1, and the BC4, were susceptible, but the BC15 was insusceptible. The results are interpreted on the basis of the assumption that the differential susceptibility is a function of the type of control of a tumor gene (Tu-Fi-Rh) endogenous to P.variatus and involved in development of fibrosarcomas and rhabdomyosarcomas. Accordingly, in P.variatus and in the F1 the Tu-Fi-Rh is controlled by repressing genes (R-genes) linked as well as non-linked to Tu-Fi-Rh; because simultaneous mutation of both R-genes following treatment with MNU is an extremely unlikely event, these genotypes have an extremely low susceptibility. By contrast, in the BC1 and the BC4 the non-linked R-genes become eliminated and only the linked R-gene remains for repression of Tu-Fi-Rh; this condition confers a high degree of susceptibility, because one single mutation may lead to impairment of the R-gene and to Tu-Fi-Rh-mediated formulation of fibrosarcomas and rhabdomysarcomas. In the BC15, furthermore, also the Tu-Fi-Rh has become eliminated, resulting in a loss of the susceptibility. The results suggest that in the xiphophophorine fish the susceptibility for responding to MNU-treatment with the development of fibrosarcomas and rhabdomysarcomas is related directly to the genotype.