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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of sodium nitrite on promotion of N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced tumors of the bladder in rats was studied. Sodium nitrite was found to promote bladder carcinogenesis, raising the occurrence of carcinomas threefold as compared to controls.
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PMID:[Sodium nitrate as a possible promotor of bladder carcinogenesis in rats]. 201 1

Sodium nitrite was shown to enhance the metabolism of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) to 7/8,9,10- and 7,10/8,9-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (tetraols) in phorbol myristate acetate (PMA)-stimulated polymorphonuclear leukocytes (PMNs). The production of these tetraols implicates the intermediate formation of the corresponding trans-7,8-dihydroxy-9,10-epoxy-7,8-9,10-tetrahydrobenzo[a]pyrene (anti-BPDE). A 2- to 3-fold increase in the tetraol yield was observed in the presence of nitrite in excess of 1 mM. Sodium azide, an inhibitor of myeloperoxidase and catalase, reduced the nitrite-stimulated metabolism of BP-7,8-diol in PMA-activated leukocytes. Diphenylene iodonium sulphate, a NADPH-oxidase inhibitor, lowered the production of tetraols in PMA-stimulated leukocytes both in the absence and presence of nitrite. Additionally, nitrite markedly enhanced the covalent binding of metabolites derived from [3H](-)-BP-7,8-diol to leukocyte proteins as well as to DNA present extracellularly. The nitrite-stimulated covalent binding to both proteins and DNA was inhibited by the presence of sodium azide. The mechanism underlying the effect of nitrite on the metabolism of BP-7,8-diol to reactive intermediates in PMA-activated human polymorphonuclear leukocytes is not known. However, the results are compatible with a peroxidase-dependent mechanism although other possible pathways may contribute to the enhanced rate of metabolism.
Carcinogenesis 1991 May
PMID:Sodium nitrite-stimulated metabolic activation of benzo[a]pyrene 7,8-dihydrodiol in human polymorphonuclear leukocytes. 202 41

Isolated calf thymus nuclei bound a chromium(III) glutathione complex in a time-dependent manner. In contrast chromium(VI) (sodium chromate) did not bind. However, when chromate was incubated with the nuclei in the presence of glutathione, chromium adducts were detected. These observations indicate that the reduction of chromate, by a reducing agent such as glutathione, is a prerequisite for the generation of bonds between the metal and constituents of the cell nuclei in vitro. Chromium adducts with nuclei are probably one cause of DNA lesions and mutations.
Carcinogenesis 1991 Jun
PMID:The reduction of chromate is a prerequisite of chromium binding to cell nuclei. 204 97

Most chemicals that produce skin cancer are genotoxic by in vitro and in vivo short-term assays and produce a high incidence of skin cancer within a year if optimal doses are applied. If in long-term skin painting studies one or two tumours in 50 mice are observed there is a general consensus that no carcinogenic activity can be claimed and it has been suggested that if up to 10% tumours are induced by irritant substances this could be due to an enhancement of spontaneous tumour incidence. Observations of skin tumour incidences higher than 10% with non-genotoxic substances, usually after a long latent period, is considered to represent evidence for a non-genotoxic mechanism. Examples of such substances include croton oil, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), sodium hydroxide, potassium hydroxide, phenol, dodecylbenzene and petroleum-derived middle distillates. Two distinct mechanisms appear to be involved in the production of tumours by a non-genotoxic substance. The first of these is that seen with the strong promoting agents. These, by binding to and activating protein kinase C, appear to directly stimulate sustained epidermal hyperplasia without severe skin damage. The other appears to involve substances producing severe skin damage either by a direct caustic effect or by cumulative irritancy. These changes give rise to marked epidermal hyperplasia with repeated episodes of regeneration and damage. The tumour induction by both mechanisms probably results from oncogene activation and it is possible that oxidative enzymes from inflammatory cells may be involved in the activation process. Various reasons are given why non-genotoxic carcinogenesis in the skin is considered not to be relevant to man and ways of recognising and avoiding its occurrence in animals studies are recommended.
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PMID:Evidence for and possible mechanisms of non-genotoxic carcinogenesis in mouse skin. 204 89

For assessment of the carcinogenic potential and the mutagenicity of dipyrone, an antipyretic anodyne, -[(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl) methylamino]-methanesulfonic acid sodium salt monohydrate, three experiments were conducted using dipyrone A produced in Japan and/or dipyrone B obtained from the Federal Republic of Germany. (i) Carcinogenic potential of dipyrone A for rat liver: 8 week old male F344 rats were pretreated with 0.01% diethylnitrosamine (DEN) in drinking water for 2 weeks and, after 1 week of resting, administered 0.4% dipyrone in drinking water, 5 days a week, for 72 weeks. After an 8 week recovery period, all surviving rats were killed at 83 weeks. Hepatocellular carcinomas developed at a higher incidence in the DEN + dipyrone group (18 of 29 rats, 62%) than in the DEN alone group (9 of 29 rats, 31%), the difference being statistically significant (P less than 0.05). No carcinogenic activity of dipyrone was demonstrated in the groups given 0.4% dipyrone for 72 weeks or 0.4% dipyrone for 25 weeks, followed by 0.05% phenobarbital (PB) for 50 weeks. However, glutathione S-transferase P positive (GST-P+) preneoplastic hepatic foci in these groups were observed at a higher incidence than in the untreated control group (P less than 0.01). (ii) Effect of dipyrone A and dipyrone B on induction of DEN-initiated GST-P+ hepatic foci in a medium-term bioassay system: 0.4% dipyrone A in drinking water and 0.57% dipyrone A or dipyrone B in powdered diet after DEN initiation had similar enhancing effects on the development of GST-P+ foci (P less than 0.001). (iii) The Ames mutation test in Salmonella: both dipyrone A and dipyrone B proved weakly mutagenic for strain TA100 in the presence or absence of S9 fraction.
Carcinogenesis 1991 Jul
PMID:Tumor promoting potential in male F344 rats and mutagenicity in Salmonella typhimurium of dipyrone. 207 Apr 86

Cytotoxicity, morphological neoplastic transformation, intracellular retention and metabolic behaviour have been investigated in BALB/3T3 Cl A 31-1-1 cells for arsenobetaine, the main form of arsenic in certain seafoods, in comparison to inorganic sodium arsenite. In order to avoid false results, particular attention was paid to the purity, checking for the presence of any trace amounts of inorganic arsenic as well as methylated contaminants in the chemically synthesized arsenobetaine. Cytotoxicity and morphological transformation assays gave obvious positive results for sodium arsenite at a dose exposure of 10 microM. On the other hand, concentrations of arsenobetaine as high as 500 microM failed to induce either cytotoxic effects or neoplastic transformations. The absence of cytotoxicity and transforming potential of arsenobetaine in comparison to inorganic arsenite can be explained by the different degree of retention and the intracellular behaviour of the two arsenic species. Cellular retention of arsenobetaine was dose dependent for exposure concentrations ranging from 1 to 500 microM with a mechanism resembling a simple diffusion (1.4 and 760 pmol of As/10(6) cells were cell associated for the two concentrations at 24 h respectively). About 95% of the intracellular arsenobetaine was present in the cytosol fraction and the attempt to detect any intracellular degradation of the organoarsenic compound failed. Thus, the low retention efficiency of arsenobetaine, its inability to interact with intracellular components and the absence of biotransformation in the cell could explain the lack of cytotoxicity and transforming potential observed in the BALB/3T3 cells. These findings reinforce the view that in humans exposed to different chemical species of arsenic the contribution to the total health risk, including the carcinogenic potential, of arsenobetaine ingested with marine foodstuffs would be negligible.
Carcinogenesis 1991 Jul
PMID:Cellular retention, toxicity and carcinogenic potential of seafood arsenic. I. Lack of cytotoxicity and transforming activity of arsenobetaine in the BALB/3T3 cell line. 207 Apr 94

The in vitro V79/metabolic cooperation assay measures the extent of gap-junctional transfer of metabolites from wild-type to mutant V79 cells. The assay is currently being explored as a short-term test to screen for tumor promoting chemicals, many of which inhibit metabolic cooperation. In this study, the assay was used to determine whether chemical interactions affect detection of tumor promoters in mixtures and to investigate types of interactions that may occur between chemicals. Several two-chemical mixtures were examined. The effects of phorbol-12-myristate-13-acetate (PMA) and phorbol-12,13-dibutyrate, two inhibitors of metabolic cooperation that operate through the same receptor-mediated pathway, were additive at concentrations below the maximally effective concentrations of either. A summation effect was observed in mixtures of two other inhibitors of metabolic cooperation, the pesticide aldrin and the principal metabolite of sodium cyclamate, cyclohexylamine. Synergistic effects were noted when PMA was combined with either aldrin or cyclohexylamine, demonstrating that chemicals in a mixture may yield a much stronger response than expected based on individual chemical exposures. Interactions were also examined between PMA, aldrin, cyclohexylamine and 2,4-diaminotoluene, a chemical that appears to enhance metabolic cooperation. 2,4-Diaminotoluene reversed effects of all inhibiting chemicals to some extent, although the pattern of response was different for each combination. In the most dramatic case, the powerful tumor promoter PMA was completely masked by 2,4-diaminotoluene. These results suggest that the V79/metabolic cooperation assay must be applied with caution in mixture testing because detection of tumor promoting chemicals can depend on other chemicals present.
Carcinogenesis 1991 Jul
PMID:Interactive effects of aldrin, cyclohexylamine, 2,4-diaminotoluene and two phorbol esters on metabolic cooperation between V79 cells. 207 Apr 95

Intravesical instillation of 2-phenyl-1,4-benzoquinone (PBQ), a metabolite of sodium o-phenylphenate (Na-OPP), at a concentration of 0.1% in saline caused acute epithelial injury, prolonged inflammation and epithelial hyperplasia in female F344 rats. Ten such instillations of PBQ within 5 weeks resulted in the development of preneoplastic lesions of the urinary bladder epithelium when followed by 5% sodium saccharin feeding for 31 weeks. Since neither urothelial damage nor tumor-initiating activity was observed with either Na-OPP itself or another metabolite, phenylhydroquinone, PBQ may play an essential role in Na-OPP urinary bladder carcinogenesis.
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PMID:Urothelial damage and tumor initiation by urinary metabolites of sodium o-phenylphenate in the urinary bladder of female rats. 211 97

The possibility that nitrofurantoin is a complete carcinogen or is an initiator or promoter of urinary bladder carcinogenesis was evaluated in male weanling F344 rats. No increase in tumor incidence was observed in rats fed nitrofurantoin at a level of 0.187% of the diet for 2 years compared to a control group. Also, no evidence of bladder initiating activity by nitrofurantoin was observed using sodium saccharin (5% of the diet) as a promoter, and no promoting activity was observed when nitrofurantoin was fed after initiation by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (0.2% of the diet for 4 weeks). In a second experiment, nitrofurantoin (at a dose of 0.187% of the diet) was administered for 6 weeks to rats with a rapidly proliferating bladder epithelium following freeze ulceration, and then the rats were treated with 5% sodium saccharin in the diet for 98 weeks. In additional rats, labelling index following [3H]thymidine injection, determined after 12 weeks of feeding nitrofurantoin, was not increased above control levels in the urinary bladder, stomach, duodenum, or liver. Metabolism of nitrofurantoin by prostaglandin H synthase (PHS) was examined using solubilized ram seminal vesicle microsomes. The rate of nitrofurantoin metabolism by PHS was much less than that observed with benzidine, and the proportion of total metabolite bound to protein was also much less than that with benzidine. These results are consistent with previous reports describing the lack of effect of nitrofurantoin on urinary bladder carcinogenesis.
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PMID:Evaluation of nitrofurantoin on the two stages of urinary bladder carcinogenesis in the rat. 211 80

Present study evaluates the chemopreventive actions of tamoxifen (10 mg/kg), retinyl acetate (50 mg/kg), tocopherol (200 mg/kg), aminoglutethimide (1 mg/kg), ergocryptine (5 mg/kg), and sodium selenite (1 mg/kg) when given singly/in combinations on the initiation of mammary carcinogenesis induced by 20 mg of DMBA in virgin female rats. DMBA was given when rats were 50 days old and the modulators were given in diet 10 days before and 10 days after carcinogen treatment and experiments were terminated 6 months later. DMBA alone yielded tumors in 62% rats. When modulators were given singly and in combinations of two, tumor incidences were not altered significantly. The range of tumor incidences was between 30% and 13% when the agents were given in combinations of 3, 4 and 5. Finally when all 6 modulators were given together the tumor incidence dropped down to 8.3%.
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PMID:Modulatory influences of tamoxifen, tocopherol, retinyl acetate, aminoglutethimide, ergocryptine and selenium on DMBA-induced initiation of mammary carcinogenesis in rats. 211 38


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