Immunostimulation exacerbates the biological effects of chemical carcinogens

The reciprocal relation between the high regenerative ability of various animal species and the low incidence of haphazard or experimentally induced malignant tumours in these animal species is well documented. Equally well documented is the repeated observation that the decline in regenerative potential coincides with an increase in the incidence of cancers, a fact which, on an evolutionary scale, parallels with the development of a sophisticated immune system. The combination of the above observations led to the hypothesis that at least parts of an immune reaction might promote tumour development, and indeed, many experiments specifically designed to answer this question support this prediction. However, this "immunostimulation theory of tumour development" is neither explained in a satisfactory fashion nor universally adopted. The aim of the present investigation was to approach this issue by exploiting the dual, spectacular ability of urodele amphibians to regenerate a lot of organs and to make a stand to carcinogenesis. To this end, urodele amphibians of the species Triturus cristatus were immunologically challenged by intra-abdominal injections of sheep serum, they had then both their hind limbs amputated, and crystals of MNNG (N-Methyl-N"-nitro-N-nitrosoguanidine) were implanted into the stumps. The results show that the effects of MNNG on the immunostimulated animals display significant quantitative augmentation with respect to non-immunized controls. This augmentation consists in higher animal mortality, extension of the dedifferentiating stump tissue and concomitant retardation of limb restoration, and increase in the incidence of abnormal regenerates.