Immunogenetics of development and its relationship to carcinogenesis.

We have been exploring the classical idea that there is a close relationship between embryogenesis and carcinogenesis. The clinical literature provides evidence for a relationship among the presence of developmental anomalies, an increased incidence of cancer, and genes linked to the major histocompatibility complex (MHC). This relationship was explored experimentally by testing the possibility that rats having the growth and reproduction complex (grc), which causes developmental abnormalities, might be more susceptible to the development of cancer following exposure to a chemical carcinogen. Two groups of animals which were genetically similar except for the presence or absence of the grc were fed the carcinogen 2-aminoacetylfluorene. The animals carrying the grc developed the morphological changes associated with early cancer of the liver, whereas their normal counterparts did not. These susceptible animals also had a number of biochemical alterations, especially in cholesterol biosynthesis, which may be associated with the development of cancer. Molecular analysis of genomic DNA by blot hybridization revealed restriction fragment length polymorphism differences between the DNA from grc and grc+ rats, and these differences may be related to the differential susceptibility of the strains to cancer.