Search

Tumor-bearing mice show a cellular sensitization to fetal antigens as detected by the macrophage electrophoretic mobility (MEM) test. Sensitization is independent of etiological and histological tumor factors. An identical state of sensitization can be found after application of chemical carcinogens (N-methyl-N-nitrosourea, benz(a)pyrene or 7,12-dimethylbenz(a)anthracene) before the tumors have developed. The results indicate that the effect is dose-dependent.

Extracts were prepared by the 3M KCl method from fetal tissues of human, mouse, cattle, pig, sheep, cat, guinea pig, and chicken origin. Lymphocytes of tumor bearing mice and tumor patients reacted specifically in the MEM-test with antigenic components of the extracts. The cellular sensitization of the tumor-bearer was not correlated with the localization and the histologic type of the tumor. The cross-reacting oncofetal antigens obviously represent phylogenetically conserved structures.

Lymphocyte reactivity to 3-M KCl extracts from fetuses of different species of origin was shown by the macrophage electrophoretic mobility (MEMB) and/or the leukocyte migration inhibition tests in tumor-bearing mice and humans. In chemical carcinogenesis, reactivity was detectable before tumors developed. Six weeks after sc injection of 1,000 micrograms benzo[a]pyrene [(BP) CAS: 50-32-8] into XVII/Bln mice, the MEMB test became positive. The latent period was 15 weeks after 1.0 micrograms BP, indicating a dose-response relationship of the phenomenon. Painting of mouse skin with 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6], croton oil (CAS: 8001-28-3), or benzene (CAS: 71-43-2) had the same sensitizing effect as BP. In contrast to the strong carcinogens BP and DMBA that caused lymphocyte reactivity to persist until tumors developed, benzene and the promoter croton oil induced only a transient effect. Termination of treatment abolished reactivity within 12 weeks. Lymphocyte reactivity to fetal extract in normal cell proliferation was evident from the fact that two-thirds-hepatectomized rats and BCG-treated mice became MEMB-positive. In hepatectomized rats the effect was reversible according to the completion of liver regeneration. Lymphocytes from tumor-bearing mice reacted with mouse and human fetal extract as well as with extracts from different developmental stages of frogs and fish. Fetal extracts were assumed to contain a phylogenetically conserved antigen.

Beads of calf serum proteins (CSB) with antigen-antibody complexes or antigen by activation with glutaraldehyde were used as immunoadsorbents for the fractionation of mouse lymphocytes. T-lymphocytes could be separated by this method with high purity. The precursors of antibody-forming cells were completely eliminated from spleen and bone marrow cell suspensions. The unspecific binding of lymphocytes to CBS or Sepharose was similar and not selective for T or B lymphocytes.

KCl extracts (3 M) from human fetuses were tested by macrophage electrophoretic mobility (MEMB), leukocyte migration inhibition, and/or leukocyte adherence inhibition techniques against lymphocytes-leukocytes from tumor-bearing humans and control persons. A positive MEMB test was found in 209 of 284 (73%) patients with various types of clinically manifest tumors. Only 15 of 134 (11%) controls gave a positive reaction by the MEMB test. Leukocyte migration was significantly inhibited in 48 of 64 (75%) tumor patients, and leukocyte adherence was significantly inhibited in 40 of 50 (80%) tumor patients versus 7 of 50 (14%) and 10 of 54 (19%) in the corresponding controls. Lymphocyte reactivity to fetal extracts is also detectable in inbred XVII/Bln, CBA/Bln, and C3H/Bln mice bearing spontaneous or transplanted tumors of different etiology. Human and mouse fetal extracts gave cross-reactions. Lymphocytes from tumor-bearing mice were reactive against fetal extracts from the cow, pig, sheep, guinea pig, cat, and chicken. Mice bearing benign skin warts induced by 7,12-dimethylbenz[a]anthracene (DMBA) as well as DMBA-treated mice without visible skin lesions gave a positive MEMB test. Likewise, pregnancy is associated with lymphocyte reactivity to fetal extracts.