European Journal of Cancer (1965)最新文献

Measurements of serum concentrations of DNA and the DNA-binding protein C3DP by radioimmunoassay showed that the levels of both substances tend to increase in cancer patients during active malignant disease. In most cases, the levels returned to normal during chemotherapy-induced remission; however, the changes in concentration for DNA and C3DP did not occur simultaneously, and no correlation was found between their levels. The sera of cancer patients contained a strong inhibitor of DNAse. We examined the possibility that C3DP may have such an inhibitory effect by binding to DNA and preventing the action of DNAse. The enzyme was fully active in the presence of purified C3DP, indicating that the DNAse inhibitor in cancer serum was a substance other than C3DP. Although the relationship between DNA and the DNA-binding protein remains unknown, their measurement may have diagnostic and prognostic value.

Experiments were carried out to study the kinetics of depopulation and repopulation of the solid transplantable rhabdomyosarcoma R1H of the rat following local irradiation with a single X-ray dose of 15 Gy. Several parameters were sequentially measured over a time interval of 25 days after irradiation: The ratio of tumour to host cells was determined by flow cytometry; the numerical density of tumour cells was obtained by stereological analysis of histological slides; the clonogenic fraction of tumour cells was assayed by plating an appropriate number of tumour cells and scoring the colonies; tumour volume was assessed by measuring two tumour diameters at right angles to each other. All parameters investigated, except tumour volume, undergo drastic changes during the first 2 weeks after irradiation. From the directly measured parameters the following values and their variation with time could be derived. The number of host cells per tumour increased by a factor of 10 within the first 10 days after irradiation, probably due to infiltration by blood-borne host cells. During the same time interval, the number of tumour cells decreased by a factor of 5, whereas the total number of cells per tumour showed an increase by a factor of 4. Since the host cells are considerably smaller than the tumour cells, the cellular numerical density increased by a factor of 3, but approached the control level by Day 18 after irradiation. From the number of clonogenic and non-clonogenic tumour cells the kinetics of repopulation and depopulation was obtained. Repopulation of irradiated tumours by surviving tumour cells as well as removal of inactivated tumour cells began immediately after irradiation and proceeded with exponential kinetics. Repopulation occurred with a doubling time of 4.4 ± 0.3 days whereas inactivated tumour cells disintegrated with a halving time of 3.5 ± 0.7 days. There were no indications that proliferation of doomed cells contributed significantly to tumour growth after X-irradiation.

Cell-specific G₁-inhibitory (chalone) activity has been extracted from old JB-1 ascites tumors and purified by means of G-15 Sephadex chromatography. Four peaks of activity were obtained, the amount of activity in each peak varying from batch to batch. The first eluting activity peak probably represents chalone activity present in an aggregated form. The latest eluting activity peak was totally unspecific and could be attributed to the presence of high amounts of salts. The two intermediary peaks of activity were investigated in more detail. It is shown that the first eluting activity peak of these two is due to the polyamine spermine complexed to a carrier. Although the spermine complex exhibits a certain degree of cell-specific inhibitory activity in vitro, it is totally inactive in vivo. The second eluting activity peak containing the main part of cell-specific G-inhibitory activity has been characterized as a small molecular weight (M_r300–600), ampholytic, hydrophobic, slightly acidic, and thiol-containing peptide active both in vitro and in vivo.

Novel transplantation antigens have been detected in a Moloney virus-induced LSTRA lymphoma of BALB/c origin (H-2^d), or in a chemically-induced L5178Y lymphoma of DBA/2 origin, following treatment of tumor-bearing hosts with 5-(3,3′-dimethyl-1-triazeno-)-imidazole-4-carboxamide (DTIC), for 4–8 transplant generations. Marked cell-mediated cytotoxic responses against DTIC-treated LSTRA or L5178Y lines were found by primary in vivo and secondary in vitro sensitization of histocompatible mice. Moreover, preliminary data show that no obvious antigenic cross-reactivity can be found among DTIC-treated sublines derived from distinct parental lymphomas. To test whether DTIC lines would express variable levels of normal histocompatibility antigens, cytotoxic lymphocytes were generated in vitro against alloantigens of H-2 complex or sub-regions of it and tested against parental or DTIC-treated lymphomas in a short-term ⁵¹Cr-release assay. A cold-inhibition test was performed with LSTRA or 4 LSTRA/DTIC sublines. The results showed that little or no difference in the expression of H-2 antigens recognized by cytotoxic lymphocytes could be detected between parental and DTIC-treated sublines. Moreover, no foreign H-2 specificities of H-2^b or H-2^k haplotypes detectable by cytotoxic lymphocytes could have been found in L5178Y or L5178Y/DTIC lymphomas.

Fifty-two rat mammary tumours were tested by radioimmunoassay for the presence of antigens related to the envelope glycoprotein gp52 and core protein p28 of the murine mammary tumour virus and found to be negative. The tumours assayed were from WAG/Rij (16 cases), BN/BiRij (16 cases) and Sprague—Dawley (20 cases) rats. Thirty of the rats had been irradiated with fast neutrons, 16 with X-rays, one had been implanted with a 17-β-oestradiol pellet and 5 were untreated. The tumours studied included 22 fibroadenomas, 2 adenomas, 19 adenocarcinomas, 4 sarcomas, 1 carcinosarcoma, and 4 of undetermined type.