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)

To learn the effects of tumor inhibitors on chemically induced malformations, caffeine, antipain, and 13-trans-retinoic acid were given to pregnant ICR/Jcl mice after a single dose of urethan, N-hydroxyurethan, N-methyl-N-nitrosourea, N-ethyl-N-nitrosourea, or 4-nitroquinoline 1-oxide, which induces about 50% of the malformed fetuses. When caffeine was given immediately after carcinogen treatment on Day 10, urethan- and N-ethyl-N-nitrosourea-induced malformations were significantly suppressed by caffeine posttreatment, while N-hydroxyurethan- and N-methyl-N-nitrosourea-induced malformations were not suppressed by caffeine. 4-Nitroquinoline 1-oxide-initiated teratogenesis was also suppressed, but not significantly so (p not equal to 0.07). The results were very similar to those of the effects of caffeine on tumors induced by these carcinogens. Malformations of genetic origin (cleft palates and cleft lips) in CL/Fr mice were also suppressed significantly by caffeine treatment on Days 8 to 11, although the level of inhibition was less than that in chemically induced malformations. A protease inhibitor (antipromotor), antipain, also suppressed urethan-induced malformations. The antiteratogenic effects of antipain were most effective when it was given during the period of 24 to 48 hr after urethan treatment, while those of caffeine were most effective when it was given immediately after urethan. The promoting process might be involved in chemically induced teratogenesis, as it was in carcinogenesis. A natural retinoid (13-trans-retinoic acid) also suppressed urethan-induced malformations. Thus, tumors and malformations induced by chemical carcinogens were suppressed by tumor inhibitors, suggesting the similarity of both processes in the subcellular level, in spite of their morphological differences.
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PMID:Antiteratogenic effects of tumor inhibitors, caffeine, antipain, and retinoic acid in mice. 641 55

The Mer- human melanoma cell line MM253c1 was treated four times with cyclophosphamide activated in situ with rat liver microsomes, the fourth cycle being preceded by treatment with the mutagenic methylating agent N-methyl-N1-nitro-N-nitrosoguanidine. The resulting subline (MM253c1-4CG) showed increased resistance to activated cyclophosphamide; the resistance of seven allogeneic human tumor lines and of a fibroblast strain spanned the two extremes represented by the autologous MM253c1 lines. MM253c1-4CG cells were highly resistant to killing by methylating agents, a property indicative of conversion to the Mer+ phenotype. Compared with the parent line, MM253c1-4CG cells were resistant to DNA cross-linking agents having different structures and transport mechanisms (melphalan, mechlorethamine, and mitomycin) and were slightly more resistant to doxorubicin, gamma rays, and hydroxyurea, but were not resistant to killing by acrolein, cytarabine, hydrogen peroxide, 254 nm UV, [3H]thymidine, or vincristine. No difference in the intracellular concentration of potential alkylation targets (RNA, protein, and SH groups) was found, and neither cell line appeared able to activate cyclophosphamide or detoxify its metabolites. Caffeine and 3-aminobenzamide had no synergistic effect upon cyclophosphamide toxicity in either cell line. 3-Aminobenzamide showed synergism with the methylating agent 5-(3-methyl-1-triazeno)imidazole-4-carboxamide, the effect being greater in MM253c1-4CG than in MM253c1 cells. These results suggest that in vitro activation of cyclophosphamide produces a metabolite similar in stability to phosphoramide mustard, resistance to such toxicity being associated not with conversion to the Mer+ phenotype but with some intracellular change with confers resistance to a variety of DNA cross-linking agents.
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PMID:Cyclophosphamide resistance developed in a human melanoma cell line. 652 97

The promoting effects of various chemicals on urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Male Fischer 344 rats were given BBN at 0.01% or 0.05% in their drinking-water for four weeks. One of the following chemicals was then administered in the diet for 32 or 34 weeks: acetazolamide, allopurinol, phenobarbital, phenacetin, ortho-phenylphenol, sodium ortho-phenylphenate, diphenyl, sodium L-ascorbate, butylated hydroxyanisole, butylated hydroxytoluene, sodium saccharin, aspartame, sodium cyclamate, stevioside, DL-tryptophan, quercetin, caffeine, nicotine and hippuric acid. Phenacetin, sodium ortho-phenylphenate, sodium L-ascorbate and butylated hydroxyanisole were significant promoters of urinary bladder neoplasia in rats initiated with BBN. Sodium saccharin, diphenyl, butylated hydroxytoluene, allopurinol, and DL-tryptophan caused moderate or slight promotion of neoplastic changes in the experimental animals. No change in tumour yield was observed after administration of the other chemicals.
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PMID:Drugs, food additives and natural products as promoters in rat urinary bladder carcinogenesis. 653 4

Food-grade natural caffeine was given in the drinking-water (available ad lib.) to barrier-maintained specified-pathogen free Sprague-Dawley rats for 2 yr. Groups of 50 animals per sex received levels of 200, 430, 930 and 2000 mg caffeine/litre, while two control groups, each of 50 animals per sex, received plain water. No unusual tumours or sites of origin for neoplastic growth were found in any animal receiving caffeine. Neoplasms found in various organs showed incidences not exceeding those seen in controls. Thus, exposure to caffeine for 2 yr did not enhance or induce neoplasia in the Sprague-Dawley rats.
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PMID:The influence of caffeine on tumour incidence in Sprague-Dawley rats. 653 87

Early alterations in normal semiconservative and repair DNA synthesis were determined in gastrointestinal tissues of HalCR mice following administration of the colon carcinogen 1,2-dimethylhydrazine (DMH). Following DMH injections of 60 and 200 mg/kg, normal DNA synthesis was rapidly inhibited in all tissues. The greatest depressions were observed in the descending colon, followed closely by the ascending colon. DNA repair was estimated by measuring unscheduled DNA synthesis. No repair was observable in the descending or ascending colon. The esophagus, forestomach, jejunum, and ileum demonstrated significant amounts of DNA repair, while the duodenum and gastric stomach displayed nominal or insignificant amounts of repair. Repair DNA synthesis was inhibited by simultaneous administration of caffeine and DMH. The degree of inhibition of normal replicative DNA synthesis and the amount of repair DNA synthesis in response to DMH treatment correlate closely with the incidence of DMH-induced tumors. Most tumors occur in the descending colon, followed by the ascending colon, and only a few in the duodenum and gastric stomach area. Neoplasms are rarely found in the remainder of the gastrointestinal system.
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PMID:Selective inhibition of replicative and repair DNA synthesis in mouse colon following administration of 1,2-dimethylhydrazine. 671 9

Clinical and photobiological differences between Japanese patients belonging to xeroderma pigmentosum (XP) variant and complementation group A were studied, especially focussing on XP variants. All of the XP variant patients commonly manifested a delayed onset of pigmented freckles as the initial symptom around 5--7 years old without acute sun erythema, in contrast to the early manifestation of acute solar erythema during infancy in XP group A patients. Six XP variant patients tested showed normal and three showed low minimal erythema doses (MEDs), at the 24 h reaction peak after monochromatic u.v. (280--330 nm) irradiation, while XP group A patients had definitely low MEDs (280--350 nm) with abnormally delayed peaking of the erythema reaction at 72 h. In cell culture studies, all XP variant strains exhibited normal levels of 254 nm u.v.-induced, unscheduled DNA synthesis (UDS), 1.4--2 times more accumulation of excision DNA breaks by arabinofuranosyl cytosine and hydroxyurea due to a subtle defect in the later polymerization step of excision repair, and a slightly higher sensitivity to u.v. cell killing than did normal cells. With respect to the synergistic effect of caffeine on u.v. lethality, XP variant strains could be divided into caffeine-susceptible (eight cases) and caffeine-resistant (two cases) subgroups. The extent of excision-break accumulation was greater in the former subgroup than in the latter. All of eight XP variant patients whose cells showed caffeine potentiation of u.v. lethality had already had skin malignancies, but two sib patients whose cells were caffeine-resistant had as yet had no neoplasm. It is strongly suggested that in XP variant, caffeine-susceptibility may be related to the development of neoplasms.
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PMID:Clinical and photobiological characteristics of Japanese xeroderma pigmentosum variant. 725 73

Six groups of male Sprague-Dawley rats were treated with phenacetin, phenazone or caffeine in the diet or with combinations of these chemicals. Another group received paracetamol in the diet and a further group received only the control diet. The rats were treated for up to 117 weeks. Renal pelvic tumors were only seen in rats treated with phenacetin or phenazone alone or in combination with caffeine, phenazone having slightly greater activity toward the urinary tract than phenacetin. Phenacetin, however, had a greater overall carcinogenic effect, inducing 31 malignant tumors. The urinary tract and the kidneys had the highest incidence of tumor followed by squamous-cell carcinomas of the head and neck. Half of the rats treated with phenacetin, phenazone and caffeine in combination developed hepatomas. The explanation may be that the addition of phenazone and caffeine altered the metabolism of phenacetin, increasing the production of N-hydroxyphenacetin, a known liver carcinogen. The justification of using phenacetin as a human analgesic must be seriously questioned, and further studies with phenazone are required.
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PMID:Carcinogenicity of analgesics: long-term treatment of Sprague-Dawley rats with phenacetin, phenazone, caffeine and paracetamol (acetamidophen). 727 56

Many tumor-promoting chemicals inhibit gap junctional communication between cells. We investigated the possibility that antipromoting chemicals may act inversely and enhance gap junctional communication. The V79/metabolic cooperation assay is an in vitro test that measures gap junctional communication indirectly by determining the extent of metabolic cooperation between mutant and wild-type V79 Chinese hamster lung fibroblasts in culture. Six in vivo antipromoters (caffeine, 3-isobutyl-1-methylxanthine (IBMX), phenidone, dibromoacetophenone, tosylphenylalanine chloromethyl ketone (TPCK), and acetic acid) were tested in this assay to assess their effects on metabolic cooperation. Caffeine, IBMX, phenidone, and dibromoacetophenone had no effect on metabolic cooperation, while TPCK slightly inhibited metabolic cooperation in one V79 assay. Acetic acid appeared to facilitate metabolic cooperation. In tests where an antipromoter was combined with the established tumor promoter phorbol 12-myristate 13-acetate (PMA), acetic acid, caffeine, and IBMX counteracted PMA-induced inhibition of metabolic cooperation, while phenidone, dibromoacetophenone, and TPCK had little effect. These results indicate that some antipromoters interfere with the ability of a tumor-promoting chemical to inhibit metabolic cooperation and suggest that alteration of gap junctional communication can be a mechanism of antipromoter action.
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PMID:Effects of selected anti-tumor-promoting chemicals on metabolic cooperation between Chinese hamster V79 cells. 751 98

Analgesic nephropathy has long been considered a potentially preventable cause of renal disease. Early reports were described in patients who consumed analgesics containing phenacetin. In recent data, the removal of phenacetin from analgesic preparations resulted in a reduction in analgesic-induced end stage renal disease in Europe and Australia. However, a reduction in the incidence of analgesic nephropathy has not occurred uniformly, suggesting that phenacetin is not the sole cause. Current data raise concerns regarding adverse renal effects of acetaminophen and nonsteroidal antiinflammatory drugs. Aspirin taken alone may be of least concern. The diagnosis of analgesic nephropathy is suggested in subjects with chronic renal failure, a history of daily consumption of analgesic preparations, small bumpy kidneys, and renal papillary necrosis or chronic interstitial nephritis. However, the spectrum of disease may be changing, because these agents also may increase the risk of cardiovascular disease and chronic renal disease due to nephrosclerosis, glomerulonephritis, and diabetes mellitus. Potential pathogenetic mechanisms in analgesic nephropathy include direct cellular injury induced by analgesics, prostaglandin inhibition with reduction or redistribution of renal blood flow, and interesting new concepts regarding the role of caffeine in increasing oxygen demand and reducing oxygen supply in the medulla. The primary goal of therapy is discontinuation of analgesic consumption. Because of the association between analgesic intake and uroepithelial tumors, surveillance of patients for neoplasm is suggested.
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PMID:Case report: analgesic nephropathy: a soda and a powder. 757 21

We studied the mechanism whereby caffeine acts as a biochemical modulator of adriamycin, and examined various methylxanthine derivitives to determine whether they would be of value as biochemical modulators. In an in vitro study of adriamycin efflux in Ehrlich ascites carcinoma cells, theophylline, pentoxifylline, and theobromine inhibited this efflux, while caffeine metabolites did not. The effects of several methylxanthine derivatives on the antitumor activity of adriamycin and on adriamycin concentration in tissue were also examined in CDF1 tumor-bearing mice. Theobromine, which inhibited adriamycin efflux in vitro, increased the antitumor activity of adriamycin and the concentration of adriamycin in tumors. The caffeine metabolites, which had no effect on the adriamycin efflux, did not increase antitumor activity. These results suggest that the metabolism of caffeine may weaken its effect as a biochemical modulator, and that pentoxifylline and theobromine would be of value as biochemical modulators of adriamycin.
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PMID:Effects of methylxanthine derivatives on adriamycin concentration and antitumor activity. 762 24


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