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Embryonic antigen expression on 2-acetylaminofluorene induced and spontaneously arising rat tumours.

2-Acetylaminofluorene induced mammary and ear duct carcinomata and spontaneously arising mammary carcinomata and sarcomata were shown to express embryonic antigens at the cell surface by their reaction with serum from multiparous female rats. These observations with essentially non-immunogenic tumours are comparable with early findings showing that embryonic antigens are also expressed on aminoazo dye induced rat hepatomata, and sarcomata induced with 3-methylcholanthrene. Re-expression of embryonal components, therefore, may be a concomitant of neoplastic transformation.

Acetamides↗

Treatment of transplanted rat tumours with double-stranded RNA (BRL 5907). I. Influenced of systemic and local administration.

Growth of transplanted rat tumours was retarded and in some cases completely suppressed when cells were injected subcutaneously in admixture with double stranded RNA (ds-RNA). This response required intimate contact between ds-RNA and tumour cells and systemic treatment with the agent failed to prevent progressive growth of a range of rat tumours. Direct cytotoxic effects of ds-RNA may contribute to tumour suppression since the compound was cytotoxic in vitro for cultured tumour cells. The involvement of host factors is suggested, however, by the in vivo tests showing variations in susceptibility to ds-RNA mediated tumour suppression similar to that previously observed with bacterial adjuvants.

Animals↗

Tumour rejection in rats sensitized to embryonic tissue. I. Rejection of tumour cells implanted s.c. and detection of cytotoxic lymphoid cells.

Wistar rats were sensitized to rat embryonic tissue by immunization with irradiated (5000 rad) rat embryo cells (2 X 10(6) s.c. + 1 X 10(6) i.p.) derived from embryos aged 14-15 days, or by implantation of irradiated (5000 rad) tissue grafts from these embryos. Three to five immunizations were given at weekly intervals, and the rats were then challenged subcutaneously 7-10 days after the final inoculum with minimal tumour-producing tumour cell doses. Immunization with irradiated rat embryo cells failed to influence the growth and development of tumour cells prepared from hepatoma D23 and D30, sarcoma Mc57, mammary carcinoma AAF57 or cells prepared from spontaneously arising mammary carcinomata Sp4 and Sp15. Using adoptive transfer techniques, lymphoid cells from embryo-sensitized rats, when used in a 3000 : 1 ratio (lymphoid cells : tumour cells), were shown effectively to retard the growth of hepatoma D23 in 3 out of 7 experiments performed. Similar adoptive transfer procedures proved ineffective in preventing the growth of mammary carcinoma AAF57. Using in vitro cytotoxicity tests, lymph node cells and spleen cells from embryo-immunized rats were shown to be cytotoxic for several rat tumour cell targets : hepatoma D23 (7/10 tests), sarcoma Mc7 (8/12 tests), mammary carcinoma AAF57 (2/2 tests) and Sp4 (3/4 tests), and for 14-15-day-old rat embryo cells (5/10 tests). In comparative tests lymphoid cells were relatively non-cytotoxic for 20-day-old rat embryo cells (1/6 tests) or cells prepared from adult rat lung or kidney (1/10 tests). The role of embryonic antigen(s) in tumour rejection is discussed.

Animals↗

Separation of spontaneous-killing effector populations by target preference.

Three populations active in human spontaneous cytotoxicity have been identified. Two of these are E-rosette positive, and differ in their adherence to nylon wool. The third is E-rosette negative. The E-rosette positive fraction which does not adhere to nylon consistently does not lyse a breast-cancer-derived target, MDA-157. When tested simultaneously on 4 other tumour target cells lines--Raji, Chang, K562 and Molt 4--however, all three populations are cytolytic. The MDA-157 target is consistently lysed by a nylon-adherent T-cell fraction, irrespective of whether the E rosettes are formed under optimal or the limiting conditions giving only "high-affinity" T cells. The observation that a given effector fraction can lyse one target but not another, whereas other fractions are cytolytic on both, implies that different targets may differentiate effector populations differing in their lytic mechanism.

Animals↗

Serum lipoproteins during chemical carcinogenesis.

1. The serum-protein and -lipoprotein patterns of rats, given a purified diet containing 0%, 0.005% or 0.03% 2-acetamidofluorene, have been determined by disk electrophoresis. 2. An abnormal high-density lipoprotein was detected from the first week of the experiment in the serum of the animals given the carcinogen. The low-density lipoproteins also increased on prolonged feeding with the carcinogen.

Animals↗

Anti-poly(A) polymerase antibodies in sera of tumor-bearing rats and human cancer patients.

Poly(A) polymerase (polynucleotide adenylyltransferase; ATP:polynucleotide adenylyltransferase, EC 2.7.7.19) was covalently linked to diazobenzyloxymethyl-filters and used to screen the sera from a number of tumor-bearing rats and human cancer patients for antibodies to poly(A) polymerase. Sera from rats that had been inoculated with any of several Morris hepatomas or a mammary adenocarcinoma contained immunoglobulins capable of complexing with poly(A) polymerase. No antibodies to the enzyme could be detected in sera from control animals or from those bearing tumors for short periods of time. Antibodies to poly(A) polymerase were also observed in sera from human patients with leukemia, polycythemia vera, and Wilms tumor. The antibodies were not evident in sera from normal volunteers or from patients with nonneoplastic diseases. These included lupus erythematosus, a disorder in which antibodies are produced against an array of nuclear proteins. Immunoglobulins from the serum of one of the human patients were capable of inhibiting poly(A) polymerase activity in vitro, whereas those prepared from the serum of a normal volunteer did not affect enzyme activity. As determined by the diazobenzyloxymethyl-filter technique, the relative concentration of antibodies in the sera of an individual with leukemia (in remission) increased severalfold during a relapse. These data suggest that the presence of antibodies to poly(A) polymerase may be characteristic of sera from cancer patients and that the relative concentration of these antibodies may be indicative of the disease state.

Adenocarcinoma↗

Occurrence of nitroso compounds in fungi-contaminated foods: a review.

Dimethylnitrosamine (NDMA), diethylnitrosamine (NDEA), methylbenzylnitrosamine, and a new N-nitroso compound, N-3-methylbutyl-N-1-methylacetonylnitrosamine (NMAMBA), were found in cornbread that was inoculated with Fusarium moniliforme and underwent an incubation and the addition of a small amount of NaNO2. The carcinogenicity of NMAMBA was shown by the induction of forestomach carcinomas and liver tumors in mice and rats. Another new nitrosamine, N-2-methylpropyl-N-methylacetonyl nitrosamine, was isolated in millet and wheat flour after similar treatment. Some species of fungi not only can reduce nitrates to nitrites but also can increase the amount of secondary amines in the moldy foods and provide favorable conditions for the synthesis of nitrosamines. Some fungi may utilize primary amines to synthesize nitrosamines in appropriate culture mediums. Furthermore, the cornmeal may naturally contain trace amounts of nitrosamines, as detected by a gas chromatography/thermoenergy analyzer. Prolonged feeding of F. moniliforme-inoculated cornbread alone also induced the development of forestomach carcinoma in rats. This indicates the occurrence of potential carcinogens, perhaps certain Fusarium mycotoxins, in the moldy cornbread in addition to the carcinogenic nitrosamines. Another nitroso compound, Roussin red methylester (di-mu-methanethiolatotetranitrosodiiron) was found in pickled vegetables that are eaten daily in the Linxian (China) area. Roussin Red may provide NO-2 ions, which would react readily with secondary amines to form nitrosamines. Possibly this compound is a natural tumor promoter and is able to induce epithelial hyperplasia of the upper digestive tract and forestomach papilloma in treated mice. Also, trace amounts of NDMA, NDEA, and some other nitrosamines were found in the extract of pickled vegetables.

Animals↗

Enhanced lymphocyte-mediated killing of tumour cells after tumour irradiation in vivo.

The effect of local X-irradiation of a syngeneic carcinoma of fibrosarcoma growing in the leg of W/Fu rats on the ability of host spleen lymphocytes to kill syngeneic and allogeneic tumour cells in vitro was examined. Lymphocytotoxicity was found to be enhanced one day after local X-irradiation (4000 R) when compared with unirradiated tumour-bearing rats (p = 0.05 to 0.01). This enhancing effect of local irradiation was not observed when the lymphocytes were tested 1 week or later after X-irradiation, nor when normal legs of non-tumour bearing rats were irradiated. Mechanisms which might possibly explain these results are a reduction in release of tumour-specific antigen which can act as an inhibitor of cell-mediated cytotoxicity, or depletion of suppressor cells in the lymphocyte population. These findings may be relavant to clinical studies of cellular immunity in patients undergoing radiotherapy of malignant tumours.

Animals↗

Dose-dependence of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) carcinogenicity in rats.

The dose-dependence of 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) carcinogenicity was investigated in F344 rats of both sexes administered the heterocyclic amine in the diet at concentrations of 25 or 100 p.p.m. for up to 104 weeks. Incidences of mammary adenocarcinomas were 7% (2/30) for 25 p.p.m. and 47% (14 of 30 rats) for 100 p.p.m. in females and those of colon adenocarcinomas were 43% (13/30) for males and 13% (4/30) for females of the 100 p.p.m. groups. No mammary adenocarcinomas were induced in males and no colon carcinomas were observed in the 25 p.p.m. groups of either sex. Furthermore, development of lymphocytic leukemia was apparently enhanced by PhIP in males. In a separate experiment, dose-dependent induction of aberrant crypts in the large intestine, considered as preneoplastic lesions, was evident after 8 weeks feeding of PhIP-supplemented diet at doses of 25, 100 or 400 p.p.m. Thus a clear dose-dependency was demonstrated for both colon and mammary carcinogenesis. Since PhIP is a particularly abundant heterocyclic amine and its carcinogenic organotropism overlaps with the types of neoplasias most commonly observed in western countries, the compound may be extremely important with respect to human cancer development.

Adenocarcinoma↗

Conversion of diets at tumor induction shows the pattern of tumor growth and metastasis of the first given diet.

In a previous study, significant differences in the growth rate of a transplantable mammary adenocarcinoma were observed between rats receiving a diet rich in saturated fatty acids (lard, diet A), and rats on a diet in which the saturated fat was partly replaced by polyunsaturated fatty acid of the omega-3 type (Menhaden oil, diet B). In the present investigation, it was our aim to study tumor growth in rats on diet A and B, as well as in rats that had, at tumor inoculation, a change of diets, from diet A to diet B. Tumor growth of rats receiving diet A throughout the whole experiment was the same as in those rats that had a conversion of diets. The data shows that the observed inhibiting effect of diet B on tumor growth could not be obtained when this diet was given exclusively after tumor inoculation.

Animals↗

The promotion of vitamin E.

Investigations that have influenced the promotion of vitamin E supplementation are reviewed. The various forms of vitamin E found in foods and the composition of synthetic vitamin E in common use are described with note of a frequent error of identification made in reports of studies on vitamin E. Recent communications on the use of antioxidants to delay carcinogenesis in animals and in humans are discussed. The publicity given the reports of cancer prevention by antioxidants will probably increase self-supplementations. It is therefore necessary to understand the pharmacological limits of such supplementation with vitamin E. Daily supplementation of adults with about 200 mg of d-alpha-tocopherol equivalents per day has not been proven to be harmful, but the effects of ingestion of more than 800 mg a day have not been studied sufficiently. Special precautions should be taken in administering emulsified vitamin E preparations intravenously to premature infants.

Animals↗

Modification of nuclear restriction in vitro by plasma from tumor-bearing animals.

Putative regulatory macromolecules, which may be useful in diagnosis or tumor detection, were identified in the peripheral blood plasma of tumor-bearing animals. We monitored the components by measuring their ability to stimulate messenger RNA (mRNA) release from isolated nuclei in a cell-free system of rat liver nuclei in fortified homologous cytosol. This in vitro test system exhibited near-normal in vivo nuclear RNA restriction. When added to the assay at a protein concentration of 3.0 mg/ml, dialyzed plasma from rats or mice with chemically induced transplantable or primary tumors stimulated mRNA release from 87% to more than 300% over control plasma from normal rats. Plasma from partially hepatectomized rats stimulated only 26% over control plasma. The test system derived from rat liver seemed to permit the monitoring of plasma from other species. Available evidence, particularly relating to tumor-host-interaction, suggests, but does not prove, that regulatory components are released from the tumor cells to the circulation.

Animals↗