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Genetic Susceptibility to Murine Hepatocarcinogenesis

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Chemical Carcinogenesis 2

Summary

Some murine strains are characterized by a high susceptibility to both spontaneous and carcinogen-induced hepatocarcinogenesis (C3H, CF-1, CBA), whereas other strains are resistant (C57BL/6, BALB/c). The liver carcinogenesis process, as well as carcinogenesis in other organs, is not a single step process, but involves multiple steps leading from the normal hepatocyte to the hepatocellular carcinoma. Therefore, genetic differences between murine strains may reside in genetic loci controlling either initiation or promotion/progression stages. We have observed, using a medium-term liver carcinogenesis bioassay and stereological analysis, that the total number of NDEA-induced liver-nodules/cm3 was about the same in a susceptible F1 hybrid (B6C3) and in a resistant one (B6C), indicating that both hybrids were equally sensitive to NDEA-initiation. However, the size of the nodules was much larger in the susceptible compared to the resistant hybrid. Therefore, we proposed that a major difference is not in the susceptibility to initiation, but in the susceptibility to progression. The hepatocytes, once initiated, grow, progress, and give rise to grossly evident tumors more efficiently and more rapidly in the susceptible than in the resistant strain. In a subsequent study we have treated B6C3F2 mice with NDEA and then measured liver nodule frequency and size, using stereological analysis. We have found that almost all mice had a similar total number of nodules/cm3. However, when the size distribution of nodules was analysed, the F2 population could be easily divided into two subgroups. The subgroups identified a population of resistant mice and another one of susceptible mice. The percentage of resistant mice was in agreement with the hypothesis that a single genetic locus accounts for the major part of the difference in the susceptibility to progression between C3H/He and C57BL/6 mice.

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Authors and Affiliations

  1. Division of Experimental Oncology, A. Istituto Nazionale Tumori, Via G. Venezian 1, Milano, Italy

    T. A. Dragani, G. Manenti, B. M. Colombo & G. Della Porta

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  1. T. A. Dragani
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  2. G. Manenti
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  3. B. M. Colombo
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  4. G. Della Porta
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  1. University of Cagliari, Cagliari, Italy

    Amedeo Columbano  & Paolo Pani  & 

  2. University of Sassari, Sassari, Italy

    Francesco Feo  & Rosa Pascale  & 

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Dragani, T.A., Manenti, G., Colombo, B.M., Porta, G.D. (1991). Genetic Susceptibility to Murine Hepatocarcinogenesis. In: Columbano, A., Feo, F., Pascale, R., Pani, P. (eds) Chemical Carcinogenesis 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3694-9_16

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  • DOI: https://doi.org/10.1007/978-1-4615-3694-9_16

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