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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biochemical properties of cyclic nucleotide phosphodiesterases in a nonmetastasizing and a spontaneously metastasizing rat mammary carcinoma were compared. The phosphooiesterases in both tumors had a pH optimum of around 8.0 and preferentially hydrolysed cyclic purine nucleotides. The rate of hydrolysis of purine nucleotides in the nonmetastasizing tumor was two times higher than in the metastasizing tumor, but the rate of pyrimidine nucleotide hydrolysis was equal in both tumors. Theophylline, caffeine, and D,L-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro20-1724) inhibited the enzyme activity in both tumors; the percent inhibition was the same by each inhibitor. The cyclic nucleotie phosphodiesterase activity in either tumor was stimulated by Mg++, Mn++, and Co++ and suppressed by Ca++, Zn,++, and Ni++. EDTA inhibited the activity below the basal level (activity in the absence of added cation), an this inhibition could be recovered up to the basal level by an equimolar quantity of either Mn++ or Mg++. Further stimulation of the enzyme activity with increasing concentrations of divalent cations was observed only with Mn++. Similar effects were observe with ethylene glycol bis(beta-aminoethyl ether)-tn,n-tetraacetic acid. The stimulatory cations affected both the low and high Michaelis constant (tkm) enzymes in these tumors by increasing the maximum velocity. In the low Km enzyme, the Km was also slightly increased. Neither guanosine 3',5'-cyclic monophosphate nor adenosine 3',5'-cyclic monophosphate had any effect on the hydrolysis of the other at physiologic levels.
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PMID:Biochemical properties of cyclic nucleotide phosphodiesterase in metastasizing and nonmetastasizing rat mammary carcinomas. 0 60

We report here that certain drugs can protect Syrian baby hamster kidney cells (BHK) in culture against the lethal agents cytosine arabinonucleoside, hydroxyurea, and colcemid. Polyoma virus-transformed BHK cells (PyBHK) are killed under the same conditions. The protective drugs include caffeine and streptovitacin A. Kinetic studies show that these drugs act specifically in G1, and that they shift BHK cells from G1 into the G0 state at the restriction point, similar to the effects of high cell density or serum deprivation. These drugs do not block the growth of PyBHK cells nearly as effectively, consistent with a reduced effectiveness of restriction point control in virus-transformed cells. Consequently, the transformed cells around their cycle and are killed by the cell cycle phase-specific toxic agents, in contrast to the arrested BHK cells. These findings provide a model for studies on differential killing of tumor versus normal cells in vivo.
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PMID:Selective killing of transformed baby hamster kidney (BHK) cells. 17 89

The activity of cyclic 3':5'-nucleotide phosphodiesterase (PDE) (EC 3.1.4.17) was measured in cultured normal and neoplastic rat mammary epithelium. Total PDE activity in normal cells was 1.6 to 6 times higher than that in tumor cells over a concentration range of 0.01 to 1 mM cyclic adenosine 3':5'-monophosphate. PDE activity was distributed between the low-speed (4000 x g) particulate and supernatant fractions in both cell lines, with the particulate fraction possessing 60 to 70% of the total. Double reciprocal kinetic plots were nonlinear, suggesting the presence of high- and low-affinity PDE activities. Similar, but not identical biphasic curves obtained from both normal and neoplastic cells suggested that at least two different PDE activities were present in a membrane-bound as well as a soluble form. Apparent Michealis constants for the high-affinity enzyme ranged from 2 to 6 muM; the low-affinity enzyme was 1 mM. In the presence of 10 mM caffeine and at a substrate concentration of 1 muM, PDE activity was inhibited 40 and 80% of basal levels in normal and tumor cells, respectively. In general, the membrane-bound enzyme was inhibited to a greater extent than the soluble, regardless of the cell line examined. Although normal cells exhibited higher PDE activities in terms of total specific activity, when soluble activities were compared at low substrate concentrations, the opposite was the case. At a substrate concentration of 0.01 muM, normal cell, low-Km soluble specific activity was 40% less than comparable tumor cell activity. Our results support the contention that PDE is induced by its own substrate, cyclic adenosine 3':5'-monophosphate. In addition, they suggest that the low cyclic adenosine 3':5'-monophosphate steady-state levels characteristic of malignant cells are maintained by a soluble high-affinity isozyme of PDE.
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PMID:Cyclic nucleotide phosphodiesterase activity in normal and neoplastic rat mammary cells grown in monolayer culture. 17 39

A well-documented rationale exists for the study of the induction of cancer at the cellular level. Transformation can be quantitated; its frequency follows a linear relationship with dose and is consistent with a "one-hit" phenomenon. Transformed colonies do produce transformed lines with attributes of neoplastic cells including the production of tumors; in vitro activity correlates with in vivo activity to provide evidence that chemically induced carcinogenesis can be studied in vitro. In vitro techniques utilizing mammalian cells in culture have made possible the rapid evaluation of carcinogenicity of agents in man's environment. Neoplastic transformation is inductive and not the result of the selection of preexisting tumor cells. The addition of a host-mediated step in the bioassay makes it possible to decrease the number of false negatives, which may result from the requirement for metabolic activation of the chemical. Thus the in vitro studies described have a high probability of providing practical methods for determining which chemicals in use have a potential of producing cancer. Furthermore, the nature of the cell-target insult interaction can be determined, as well as the chemical nature of the ultimate carcinogen, the degree to which any agent acts alone, be it a chemical, a virus, or irradiation, and the extent to which one agent interacts with another from the same or a different category of carcinogens. Sequential treatment involving chemicals, viruses, and radiation are important, since combinations of various agents may be responsible for an increased risk of cancer in laboratory animals and human populations. The use of multiple agents may also lead to different but specific new types of assays to use for surveillance of our environment for carcinogenic agents. Pretreatment of Syrian golden hamster embryo cells with either X-irradiation or methyl methanesulfonate, but not UV-irradiation, increases the frequency of chemical transformation as does posttreatment with caffeine. Most, if not all, chemical carcinogens will increase the sensitivity of hamster embryo cells to transformation by a carcinogenic simian adenovirus SA7. The enhancement of virus transformation is related to both the length of chemical treatment and the interval between chemical and viral addition. The mechanism of transformation enhancement by various agents has yet to be explained. They may affect a number of molecular processes or cause a modification of existing DNA and thus provide an explanation for carcinogenesis; in fact, in some systems some of these agents may also show mutagenic activity and produce chromosomal aberrations, However, although DNA is the critical site for a mutagen, the critical target(s) of chemical carcinogens is still unknown.
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PMID:In vitro carcinogenesis with cells in early passage. 37 16

The i.p. injection of caffeine (8, 20, and 40 mg/kg) 3 times weekly for 8 weeks suppressed the development of spontaneous pulmonary adenomas in strain A mice. The same caffeine injection scheme suppressed urethan (0.25 and 1.0 mg/g)-induced lung tumor development when caffeine treatment started 1 week before urethan administration, but this suppression was not significant when caffeine treatment was initiated 1 week after urethan injection. The most pronounced suppression of lung tumor formation occurred when caffeine was given as only two injections 3 hr before and 3 hr after urethan administration. The incorporation of [3H]thymidine into lung tissue DNA of caffeine-treated mice was impaired at the time of urethan administration. Also, caffeine partially antagonized the effects of urethan on lung tissue, as measured by [3H]thymidine incorporation studies. One interpretation of these results is that caffeine-induced suppression of DNA synthesis interferes with pulmonary adenoma induction by decreasing the affinity of lung tissue DNA for urethan. The finding that chronic caffeine treatment produced continued suppression of [3H]thymidine incorporation into lung tissue DNA suggests that caffeine-induced inhibition of spontaneous pulmonary adenoma formation is due to a general suppression of lung DNA-synthetic activity.
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PMID:Inhibiting effect of caffeine on spontaneous and urethan-induced lung tumors in strain A mice. 64 85

A survey and discussion are presented of plants classified as Spermatophyta and Pteridophyta, extracts of which have been shown to be oncogenic or tumor-promoting in animals. The active oncogenic and tumor-promoting principles, where known, have been identified. They represent tannins; pyrrolizidine, indole, tropolone, quinoline, purine, and benzophenanthridine alkaloids; nitroso compounds; triterpene glycosides; lignans; isoflavans; allyl benzenoids; simple (nu-pyrenes; and carbocyclic hydroxy acids. A total of 28 compounds of known structure have been identified as oncogens and several phorbol esters as tumor-promoters. Plants known to contain any of the 28 oncogens (excluding shikimic acid and caffeine) have been tabulated; they represent at least 454 species, 110 genera, and 34 families of Spermatophyta and Pteridophyta.
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PMID:Oncogenic and tumor-promoting Spermatophytes and Pteridophytes and their active principles. 79 86

The anti-tumor agent cis platinum (II) diammine dichloride (cis Pt(II)) caused chromosomal abnormalities in Chinese hamster V79-379A cells. The time of appearance of these abnormalities suggested that they arise as a consequence of DNA synthesis on a damaged template. The yield and severity of chromosomal abnormalities was greatly enhanced by a non-toxic concentration of caffeine, and this enhancement was associated with a potentiation of cis Pt(II) induced cell death. These results suggest that damage to DNA which arises from cis Pt(II) treatment can be repaired in this cell line by a caffeine-sensitive post-replication repair process.
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PMID:Post-replication repair of DNA in Chinese hamster cells treated with cis platinum (II) diamine dichloride. Enhancement of toxicity and chromosome damage by caffeine. 124 May 92

The constitutively class I-negative tumor cell line, Kgv, expresses H-2Dk in response to interferon-gamma (IFN-gamma), but not in response to IFN-alpha/beta, tumor necrosis factor, or lymphotoxin. H-2Dk expression was not induced on Kgv cells by the methylxanthines, pentoxifylline (PTX) and caffeine, which modulate class I expression on cells that constitutively express class I molecules. Treatment of Kgv cells with either IFN-alpha/beta, PTX, caffeine, or dibutyryl cAMP and a concentration of IFN-gamma insufficient by itself to induce Dk expression resulted in the induction of Dk expression. Since PTX and caffeine are cAMP-specific phosphodiesterase inhibitors, it is possible that the effects of PTX, caffeine, and dibutyryl cAMP involve a cAMP-dependent mechanism. We conclude that concentrations of IFN-gamma insufficient to induce Dk expression on Kgv cells may be capable of rendering the Dk gene responsive to signals that, in the absence of IFN-gamma treatment, have no effect on Dk expression.
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PMID:Interferon-alpha/beta, pentoxifylline, and caffeine synergize with interferon-gamma to induce major histocompatibility complex class I expression on a constitutively class I-negative murine tumor cell line. 128 7

Chlorpromazine is now emerging as an adjuvant chemotherapeutic agent for the treatment of neoplasia. This was further supported in the present study by the following lines of evidence: it was shown that chlorpromazine causes damage in a series of native nucleic acids, though at somewhat high concentrations. Furthermore, chlorpromazine and caffeine were shown to act synergistically to potentiate the cytogenetic effect of adriamycin on human lymphocytes in vitro and on Ehrlich ascites tumour (EAT) cells in vivo. It is suggested that chlorpromazine alone or in combination with caffeine may exert its cytotoxic effect on normal and neoplastic cells not only indirectly, i.e. by facilitating the intracellular retention of adriamycin, but also directly by intercalating into nucleic acids.
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PMID:Chlorpromazine-induced damage on nucleic acids: a combined cytogenetic and biochemical study. 137 Jul 14

In recent years there has been increasing interest in antimutagenesis, and studies have been done using both prokaryotic and eukaryotic systems. In eukaryotic systems the first studies were performed with different strains of Schizosaccharomyces pombe. In particular, caffeine and L-methionine were investigated. Different strains of Saccharomyces cerevisiae were employed in studies of a wide variety of compounds, including acridine, saccharin, salts, tumor promoters and co-carcinogens. Strain D7 was widely employed and antimutagenic activity of spermine, chlorophyllin, cobaltous chloride and fermented milk is reported.
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PMID:Antimutagenicity in yeast. 137 21


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