Summary
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 susceptibilities 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 well as their F 1 proved to be insusceptible; while from the three backcrosses, which were tested, namely the BC 1, BC 4 and BC 15, both the BC 1 and the BC 4, were susceptible, but the BC 15 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 BC 1 and the BC 4 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 formation of fibrosarcomas and rhabdomyosarcomas. In the BC 15, 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 rhabdomyosarcomas is related directly to the genotype.
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Dedicated to Curt Kosswig on the occasion of his 75th birthday
Supported by Deutsche Forschungsgemeinschaft through Sonderforschungsbereich 103 „Zellenergetik und Zelldifferenzierung“, Marburg (C9 and C1O), and by Justus-Liebig-Universität Gießen
S.Abdo is on leave from University of Alexandria, Egypt, supported by the Egypt Ministry of Education. This paper contains parts of her dissertation
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Schwab, M., Abdo, S., Ahuja, M.R. et al. Genetics of susceptibility in the platyfish/swordtail tumor system to develop fibrosarcoma and rhabdomyosarcoma following treatment with N-methyl-N-nitrosourea (MNU). Z. Krebsforsch. 91, 301–315 (1978). https://doi.org/10.1007/BF00312292
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DOI: https://doi.org/10.1007/BF00312292