Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Schistosomiasis has long been associated with cancer. This association is most prevalent between Schistosoma hematobium and bladder cancer. Numerous theories have been proposed to explain the causal link between the parasite infestation and the ensuing neoplasia. One theory that has not received as much attention as others, however, is the role of genotoxins in the neoplastic process. Considering the substantial amount of supportive evidence for the cocarcinogenic effects of schistosomes, concern for the health effects resulting from exposure of infested individuals to either exogenous or endogenous genotoxins is certainly warranted.
Environ Mutagen 1985
PMID:Schistosome related cancers: a possible role for genotoxins. 389 33

Nitrogen mustard (N-mustard) inhibits the ouabain-sensitive and the furosemide-sensitive Rb uptake of Ehrlich ascites tumor cells, whereas the transport, which is resistant to both inhibitors, is not affected by the alkylating agent. At N-mustard concentrations below 10 microM, the reduction in Rb uptake is predominantly due to an interference with the furosemide-sensitive system. The dose response curve for the inhibition by N-mustard of the furosemide-sensitive Rb uptake closely parallels the dose response curve for the anti-tumor activity of the alkylating drug. This is in contrast to the behaviour of the ouabain-sensitive Rb transport. The inhibition of the furosemide-sensitive Rb uptake is expressed much less in cells which are resistant to N-mustard. The recovery of the furosemide-sensitive transport system after a single exposure to N-mustard is relatively slow and characterized by an initial 4 h lag period, whereas the repair of DNA-interstrand cross-links starts immediately after removal of the drug. At mM concentrations furosemide blocks the multiplication of Ehrlich ascites tumor cells. However, lower concentrations of furosemide which cause a 50% reduction in the furosemide-sensitive Rb uptake do not interfere with cell proliferation. This is in contrast to the behaviour of N-mustard which exerts a clear-cut depression of cell growth at concentrations leading to a 50% inhibition of the furosemide-sensitive Rb transport. It is concluded, therefore, that the inhibition of the furosemide-sensitive system alone is not sufficient to explain the anti-tumor activity of the alkylating agent. The effect is discussed as part of a more extended N-mustard-induced membrane alteration which may be important for the growth inhibitory effect of the alkylating agent.
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PMID:Nitrogen mustard interference with potassium transport systems in Ehrlich ascites tumor cells. 401 67

The kidney is a key target tissue in animal and human carcinogenesis, yet there are no established short-term tests for studying the genotoxicity of chemicals in the kidney. We have developed an assay for the measurement of chemically induced DNA repair as unscheduled DNA synthesis (UDS) in isolated rat kidney cells following in vivo treatment. Male Fischer-344 rats were injected intraperitoneally with chemicals dissolved in saline or corn oil. After various treatment times, the kidneys were perfused with a collagenase/trypsin solution (CTS), minced into small pieces, and stirred in CTS at 37 degrees C for 1 hr to dissociate cells. Cultures contain a high proportion of epithelial cells from the proximal and distal tubules. Cultures were incubated for 16-18 hr with 3H-thymidine in Williams' Medium E supplemented with 20% fetal bovine serum. UDS was measured by quantitative autoradiography as net grains/nucleus (NG). The percentage of cells in repair (% IR) was defined as the percentage of cells with greater than or equal to 3 NG. Saline- or corn oil-injected controls consistently produced -3 to -5 NG with less than 1% IR. The time course of DNA repair following treatment with the direct-acting mutagen methylmethane sulfonate (MMS) or the renal carcinogen azaserine showed a peak response at 2 hr after treatment. Azaserine showed a rapid decline in UDS at 12 and 24 hr, whereas MMS exhibited a relatively high UDS level at 24 hr. The renal carcinogens methylazoxymethanol acetate, N-methyl-N-nitrosourea, and streptozotocin all yielded strong positive UDS responses. The liver and intestinal carcinogen 1, 1-dimethylhydrazine at doses up to 50 mg/kg was cytotoxic to kidney cells, but induced less than 0 NG. Treatment with 1,2-dimethylhydrazine, which induces kidney tumors in mice but not rats, also induced less than 0 NG. Treatment with o-anisidine, a weak renal carcinogen, did not induce UDS in the kidney, suggesting that it may be acting as a tumor promoter. These results demonstrate the usefulness of this assay for the detection and study of a variety of genotoxic kidney carcinogens.
Environ Mutagen 1985
PMID:Measurement of unscheduled DNA synthesis in rat kidney cells following in vivo treatment with genotoxic agents. 406 62

Mouse epidermal cell lines have been identified which respond to tumor-promoting (but not nonpromoting) phorbol esters with an irreversible shift in anchorage independence, an in vitro marker of neoplastic phenotype. This response may be analogous to a later stage of tumor promotion in vivo. The shift occurs at TPA concentrations as low as 0.1 ng/ml (1.6 x 10(-10) M). The specificity of the soft agar growth response is not limited to phorbol esters but extends to nonphorbol plant diterpenes such as mezerein, to detergents, to polycyclic hydrocarbons present in cigarette smoke, and to some growth factors. All of the above classes of compounds have been previously shown to have tumor-promoting and/or cocarcinogenic activity in mouse skin in vivo. Clonal heterogeneity for TPA responsiveness has been found. Clones which were highly responsive to phorbol esters were also highly responsive to other classes of promoters, indicating their usefulness both for promoter detection and mechanism studies. The anchorage-independence to response to TPA was inhibited by a series of retinoids whose activity paralleled that for inhibiting tumor promotion in vivo. Both retinoid inhibition and clonal heterogeneity for promoter response are being utilized to study determinants of preneoplastic progression.
Teratog Carcinog Mutagen 1980
PMID:A cell culture assay for tumor-promoter-dependent progression toward neoplastic phenotype: detection of tumor promoters and promotion inhibitors. 611 3

Cell culture systems that respond to the combined action of initiating chemical carcinogens, tumor promoters, and transforming viruses represent useful model systems for studying the complex multifactor nature of the carcinogenic process. We have utilized both secondary rat embryo (2 degrees RE) and a clonal population of established Fischer rat embryo (CREF) cells to study the effect of multiple agents on the process of adenovirus transformation. In the present review we summarize our investigations on the effects of polycyclic aromatic hydrocarbons, tumor promoters, a bee venom polypeptide-melittin (MEL), and the polypeptide hormone epidermal growth factor (EGF) on transformation of rat embryo cells by a temperature-sensitive mutant of human adenovirus type 5 (H5ts125). We also describe the effect of tumor promoters on the progression of the transformed phenotype, ie the temporal acquisition of anchorage-independent growth in adenovirus-transformed clones and the ability of MEL and EGF to elicit effects similar to those of tumor promoters in adenovirus-transformed cells.
Teratog Carcinog Mutagen 1980
PMID:Interactions between initiating chemical carcinogens, tumor promoters, and adenovirus in cell transformation. 611 15

A mechanistic link between teratogenesis and carcinogenesis has been suggested by a wide variety of scientific observations. This report attempts to provide a theoretical explanation for one of the several possible mechanisms which might be shared during carcinogenesis and teratogenesis. The initiation and promotion concept of carcinogenesis was briefly reviewed and the role of intercellular communication during the complex tumor promotion phase was discussed. Inhibition of intercellular communication by a wide variety of physical, chemical and biological factors was speculated to disrupt the regulation of proliferation and differentiation in stem cells. Chemicals, which interfered with intercellular communication during early organogenesis, have the potential of being teratogens, while if they are present in the developed, initiated organisms have the potential of being tumor promoters. Evidence was presented showing that known tumor promoters which inhibited intercellular communication also had been shown to be teratogens. It was concluded that in vitro assays, designed to measure intercellular communication, although having known limitations, might be used as an in vitro means to screen for potential teratogens.
Teratog Carcinog Mutagen 1982
PMID:The role of inhibited cell-cell communication in teratogenesis. 612 78

Dose-response data from experimental and epidemiologic carcinogenicity studies were analyzed in attempts to resolve basic questions in extrapolating from high to low doses and assessing human risk. Four models (Weibull, Mantel-Bryan, Marshall-Groer, and Mancuso-Stewart) were fit to 46 sets of experimental and 4 sets of epidemiologic data by maximizing the likelihood function with a Rosenbrock hill-climbing algorithm. The models were compared as to their adequacy in describing the data and analyzed to determine the effect of carcinogen and breeding category, species, and spontaneous tumor incidence. The shapes of the dose-response curves were analyzed, and errors in risk estimation from linear extrapolation through the origin were calculated. All models were shown to fit the data and to be comparable in accuracy. The dose-response curves were generally "stretched out," particularly for outbred strains, with one or two orders of magnitude of dose increase required to increase the proportion of tumor responders from 10% to 70%. Linear extrapolation through the origin generally underestimated the response at low doses, frequently by several orders of magnitude. The power dependence of tumor incidence on dose was generally found to be of the order of unity, substantially less than assumed in most mathematical models.
Teratog Carcinog Mutagen 1982
PMID:Analyses of carcinogenesis dose-response relations with dichotomous data: implications for carcinogenic risk assessment. 612 38

Mesenchymal cells from the prefusion human embryonic palate have been established in culture and can be grown in either a serum-free hormone-supplemented medium or a serum-containing medium. The growth of these cells is quite rapid in culture and inhibited in a dose-dependent manner by most teratogens thus far tested, such as dexamethasone. These cells are highly sensitive to a variety of DNA synthetic and mitotic inhibitors. The responses of these cells are complementary to the ovarian tumor cell attachment assay of Braun et al [1, and in this volume]. When used in conjunction with the tumor cells, the overall reliability is greater than 90% with only one false-negative, allopurinol.
Teratog Carcinog Mutagen 1982
PMID:Prescreening for environmental teratogens using cultured mesenchymal cells from the human embryonic palate. 613 Jun 30

Endodermal cells isolated from the yolk sacs of day 3 chick embryos were able to activate metabolically cyclophosphamide. This was demonstrated by the cytotoxicity of cyclophosphamide to the endodermal cells themselves as well as by the ability of endodermal tissue to mediate a cytotoxic response in coculture with KB cells, a human tumor cell line unable to activate cyclophosphamide. Yolk sac endodermal cells from day 3 embryos were sensitive to cyclophosphamide when the drug was added immediately after the start of culture, but not when the drug was added after 24 hr of culture. The ability to metabolize cyclophosphamide by the day 3 embryo appeared limited to the endodermal cells of the yolk sac as cells derived from neither the embryo proper nor yolk sac mesoderm-ectoderm tissue were positive in these tests. Using whole blastoderms, cyclophosphamide activation was detected as early as 12 hr of egg incubation.
Teratog Carcinog Mutagen 1984
PMID:Metabolic activation of cyclophosphamide by yolk sac endodermal cells of the early chick embryo. 614 29

The attempt has been made recently to categorize carcinogens into two mechanistic types based on their mechanism of action: genotoxic (capable of reacting with and damaging DNA) and epigenetic (unable to damage DNA to any detectable extent). By requiring that a given chemical fit into one or the other of these narrowly defined categories for regulatory purposes, we are probably oversimplifying potential biological effects. In fact, based on our limited understanding of carcinogenic mechanisms, this artificial distinction should probably be abandoned in favor of a more precise statement of each chemical's mechanism or relative potency of initiating and promoting effects. Since the standard short-term tests by which carcinogenicity of chemicals is screened were designed to detect certain chemical classes with active electrophilic intermediates, weak or specialized carcinogens may be missed and may be assumed erroneously to be nongenotoxic. The mechanisms of carcinogenicity for such carcinogens may include particulate deposition, active radical formation, liver toxicity, and hormonal interactions. Not all of these secondary mechanisms depend upon a detectable level of binding to DNA, damage to DNA, or modification of the DNA sequence, even though they may demonstrate other characteristics of a complete carcinogen (that is, irreversibility and lack of a threshold). Certain agents have been labeled as epigenetic. However, a consideration of the literature on sample agents (diethylstilbestrol, asbestos, and urethane) reveals that these are not epigenetic carcinogens despite their being labeled as such. Agents with irreversibility and no threshold have initiating potential and, as such, are genotoxic, whereas carcinogens that are classified as nongenotoxic are largely agents that promote the growth of liver tumors. Even promotion can be a mechanistically specialized phenomenon. For example, some promoters are cytotoxic to the liver, but not all liver toxins are liver tumor promoters or liver carcinogens. Further, the carcinogens commonly labeled as epigenetic might cause a unique specialized genotoxicity not detected by common screening tests routinely used for detecting genotoxicity. If we assume that this unrecognized but necessary initiating potential is mediated by some specialized genotoxicity, extra care must be taken to establish a genuine lack of genotoxicity before an agent can be classified (and regulated) as a promoter (lacking the ability to initiate tumor growth but still enhancing tumor development).(ABSTRACT TRUNCATED AT 400 WORDS)
Teratog Carcinog Mutagen 1984
PMID:Implications of multiple mechanisms of carcinogenesis for short-term testing. 615 Dec 60


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