Fetal pancreatic antigens in the Syrian golden hamster and their relationship to development and carcinogenesis.

A rabbit antiserum raised against pancreatic extracts of newborn Syrian hamsters was used in a histological study of pancreas development. This antiserum, after being rendered specific by appropriate absorption, stained the cytoplasm of acinar cells in neonatal pancreas. The reaction was observed from the 13th day of gestation (3 days before delivery) until the 10th day after birth. This period was characterized by a progressive maturation of the endocrine pancreas. The disappearance of fetal pancreatic antigens coincided with the appearance of Langerhans islets. Adult pancreas was not stained with the antiserum, but a good reaction was observed in chemically induced pancreas adenocarcinomas. All reactions were confirmed by immunochemical studies. Polyacrylamide gel electrophoresis followed by immunodetection on nitrocellulose blots demonstrated the presence of two major fetal antigens. Thus, this study demonstrates the existence of fetal pancreatic antigens associated with development which are reexpressed in pancreatic tumors.

Evolution of DNA polymerase alpha, beta and terminal deoxynucleotidyl transferase in hamster lymphoid populations during the development of different types of tumors.

We followed the evolution of DNA polymerase alpha, beta and terminal deoxynucleotidyl transferase (TdT) in the thymus, spleen and bone marrow of tumor bearing hamsters. Tumors were induced by spontaneously transformed fibroblasts (EHB), by SV40 (ZD) or by 20-methylcholanthrene (MCH2) transformed fibroblasts. We have shown that, in the thymus, the TdT activity of the various tumor bearing hamsters is generally inferior to the TdT activity of the control. In the spleen of animals bearing viral or spontaneously induced (ZD or EHB) tumors, the TdT activities were higher than in the controls. Moreover, DNA polymerase alpha and DNA polymerase beta activities in the spleen of the EHB tumor bearing hamsters were higher than in the controls. This fact, however, was not observed in the two other kinds of tumor, possibly because EHB tumors were growing much faster and led to earlier changes in DNA polymerases activities, as well as in spleen size and cellular populations. Finally, in the bone marrow, TdT, polymerase alpha and beta of ZD and EHB tumor bearers reached much higher activities than in the controls; for the MCH2 tumor bearing hamsters, no difference with the controls could be observed.

[Cellular and humoral response to tumor antigens in the hamster]. / Réponse cellulaire et humorale aux antigènes tumoraux chez le hamster

Studies on the histological of the lympoid organs and the evolution of the immune response were done during the growth of a tumour induced by SV40 transformed cells. The immune response was characterized by a high level of circulating antibodies and presence in the thymus and spleen of lymphoid cells containing IgG with antibody function.

Humoral and cellular immune response during the growth of an SV40 induced tumour in hamsters.

Hamster fibroblasts transformed in vivo by the SV40 virus (TSV5Cl2) induce tumours when injected into adult hamsters and antibodies present in sera of tumour-bearing animals are used to demonstrate the presence of the antigens specific for the viral transformation. These tumours are a very useful tool in studying the evolution of the immune response during the tumour growth. A systematic histological examination of the spleen, thymus and lymph nodes was undertaken and the results thus obtained were correlated with a parallel study of the cells of the peritumoral region, the thymus and the spleen by immunofluorescence using antisera of different specificities. We were able to show that the plasma cells which make up the early peritumoral reaction and the lymphoblasts found later in spleen and thymus both synthesize antibodies directed against virus induced antigens. Circulating antibody directed against the same antigens is first detected at/or about the time that the peritumoral plasma cell reaction disappears and increases progressively as tumour weight increases.

Detection of pancreas pretumoral stage by means of organ transplantation.

Syrian golden hamsters were treated at monthly intervals for three months with N-nitrosobis (2-oxopropyl) amine (BOP) at doses of 20 mg/kg. During the treatment program individual pancreases were analysed by histology and transplanted into syngeneic recipients. Within the first 20 weeks following BOP administration, only a few alterations in the acinar cells were detected histologically. Nevertheless, pancreases taken as early as 10 weeks following the initiation of the chemical treatment produced local tumors at the site of subcutaneous implantation. Tumors thus obtained by graft were noted to be carcinomas of ductal type. Organ transplantation was thus observed to be a good method of detecting early neoplastic transformations in the pancreas which were not seen by conventional histology.