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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 lithium carbonate on promotion of N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced bladder tumors in rats was studied. Lithium carbonate acted as promoter in bladder carcinogenesis resulting in a 6-fold increase in the tumor occurrence as compared to controls. The experiments with sequential injection of the agent showed its promoting effect to be most apparent within 3-6 months following exposure to the carcinogen.
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PMID:[The lithium carbonate promotion of urothelial tumors in rats induced with N-butyl-N-(4-hydroxybutyl)-nitrosamine]. 134 60

The effects of low, adequate, and supplemental intake of calcium and vitamin D3 on 12-O-tetradecanoylphorbol-13-acetate (TPA) skin tumor promotion were examined. Administration of the experimental diets was started one week before the first TPA application to the 7,12-dimethylbenz[a]anthracene-initiated dorsal skin of female Sencar mice. Neither dietary calcium in a range from 0.15% to 2.0% of the diet as calcium carbonate nor vitamin D3 ranging from 200 to 4,000 IU/kg diet resulted in modulation of the skin papilloma response in terms of incidence, number per mouse, or size distribution of tumors. There were also no effects of the varied levels of calcium or vitamin D3 on mouse body weights, serum calcium, or TPA induction of epidermal ornithine decarboxylase activity. These results indicate that dietary administration of a wide range of doses of calcium or vitamin D does not alter the serum calcium levels and, therefore, does not appear capable of altering skin tumor promotion. These results are in contrast to reports that demonstrate antineoplastic activity for both calcium ion and active hormonal vitamin D, either in control of epidermal cell proliferation and/or differentiation or inhibition of carcinogenesis.
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PMID:Effects of dietary calcium and vitamin D3 on tumor promotion in mouse skin. 166 12

Ion transport across premalignant large bowel mucosa in CF1 mice was evaluated by measuring sodium and chloride fluxes across voltage-clamped colonic segments obtained from control animals and animals treated for 4 wk with the procarcinogen 1,2-dimethylhydrazine, which induces tumor development principally in the distal colon. In control CF1 mouse colon, the net flux of sodium was 5.1 +/- 0.7 and 4.6 +/- 0.7 microEq.cm-2.h-1 and the net flux of chloride was 6.1 +/- 1.3 and 0.8 +/- 1.2 microEq.cm-2.h-1 in the distal and proximal colon, respectively. Removal of bicarbonate decreased the net flux of sodium 1.5 +/- 0.5 and 1.9 +/- 0.7 microEq.cm-2.h-1 in the distal and proximal colon, respectively, while the net flux of chloride was decreased to 1.7 +/- 1.8 microEq.cm-2.h-1 in the distal colon but was unaltered (0.8 +/- 0.1 microEq.cm-2.h-1) in the proximal colon. Addition of 25 mM bicarbonate stimulated the net flux of sodium and chloride absorption in the distal colon but increased net flux of sodium absorption alone in the proximal colon and stimulated net flux of chloride secretion. Removal of chloride decreased net flux of sodium to 3.4 +/- 1.4 and 1.8 +/- 0.8 microEq.cm-2.h-1 in the distal and proximal colon, respectively. Addition of 20 mM Cl stimulated net flux of sodium in the distal but not the proximal colon. These data suggest that sodium absorption is mediated by an electroneutral Cl-dependent, HCO3-dependent process (i.e., Na-H Cl-HCO3 dual exchange) in control distal colon and by an electroneutral HCO3-dependent process in control proximal colon. Following 1,2-dimethylhydrazine treatment, net flux of sodium in the distal colon was not stimulated by the addition of Cl or HCO3, and transport in the proximal colon was similar to that in control animals. However, 1,2-dimethylhydrazine treatment appears to uncouple Na-H Cl-HCO3 exchange in the distal colon early in the process of large bowel carcinogenesis.
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PMID:Uncoupling of sodium chloride transport in premalignant mouse colon. 169 47

The effect of calcium carbonate (CaCO3) on the initiation of gastroduodenal carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was examined under the conditions with and without sodium chloride. Male Wistar rats were given drinking water containing MNNG (100 mg/liter) and one of the following diets during the first 20 weeks ad libitum. Group 1 was given basal diet; group 2, diet with 10% NaCl; group 3, diet with 10% NaCl and 2.5% CaCO3; group 4, diet with 10% NaCl and 7.5% CaCO3; group 5, diet with 7.5% CaCO3. During the next 20 weeks, all groups were fed with the basal diet and tap water. The carcinogenic incidences of glandular stomach between the nonsalted diet groups, 1 and 5 (15% and 16% respectively), were not significantly different at the 40th week. The incidences in the salted diet groups 2, 3, and 4 were 59, 63, and 43%, respectively, indicating no statistical difference among them. Thus, CaCO3 showed no anticarcinogenic effect on gastroduodenal carcinogenesis. In the groups 3 and 4, however, increased incidence of duodenal cancer was observed.
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PMID:Effect of calcium on rat gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine. 181 37

Experiments from different laboratories have shown that benzoyl peroxide (BzPo) and other organic peroxides are effective tumor promoters in the mouse skin two-stage carcinogenesis system. In the present paper we have studied the short-term effect of six other organic peroxides, which have not been previously assayed as skin tumor promoters. These compounds were chosen for their molecular diversity, the type of radical predicted to be formed, solubility and availability. The parameters evaluated in this study include a series of short-term markers of tumor promotion, hyperplasia, induction of dark basal keratinocytes and induction of ornithine decarboxylase activity. After single applications the biological activity of the compounds was: m-chloroperoxybenzoic acid greater than di-m-methylbenzoyl peroxide greater than dicumyl peroxide greater than O,O-t-butyl-O-(2-ethylhexyl)mono-peroxycarbonate greater than benzoyl peroxide greater than di-m-chlorobenzoyl peroxide greater than di-t-butyl peroxide greater than t-butyl hydroperoxide. After multiple applications, the order of activity of the compounds was: dicumyl peroxide greater than di-m-methyl-benzoyl peroxide greater than O,O-t-butyl-O-(2-ethylhexyl)monoperoxy carbonate greater than m-chloroperoxybenzoic acid greater than di-m-chlorobenzoyl peroxide greater than t-butyl hydroperoxide greater than benzoyl peroxide greater than di-t-butyl peroxide. The difference of activity among the different compounds did not seem to correlate directly with the chemical stability of the compound; it is more likely that the activity depends on different factors such as percutaneous absorption, metabolism, and the rate of free radical formation in vivo. The data presented here further support the association between free radicals and tumor promotion since all of the compounds, with the exception of one, were active in inducing the short-term markers of tumor promotion. It will also establish conditions for future tumor experiments.
Carcinogenesis 1991 Apr
PMID:Induction of short-term markers of tumor promotion by organic peroxides. 201 21

Changes in urinary parameters (particularly electrolyte levels and pH), and DNA synthesis and the morphology of the bladder epithelium were investigated in rats that were fed for 4 or 8 wk on diets containing various Na, K, Mg or Ca carbonate salts, with or without L-ascorbic acid (AsA). [The carbonate salts were fed at a level of 3% in the diet, and AsA or AsA-Na was administered at 5% in the diet. NH4Cl was at 1% in the diet.] The effects of treatment with NH4Cl (used as a urine acidifier), and of combined treatment with sodium ascorbate (AsA-Na) and NH4Cl were also investigated. Urinary pH was significantly elevated in groups given NaHCO3, K2CO3, AsA + NaHCO3, AsA + K2CO3 and AsA-Na, whereas treatment with AsA or NH4Cl alone caused a significant drop in urinary pH. An increase in urinary electrolytes or ascorbic acid was associated with the corresponding dosing regimen. DNA synthesis in the bladder epithelium was increased in groups given NaHCO3, K2CO3, AsA + NaHCO3, AsA + K2CO3 or AsA-Na. Furthermore, all treatments that induced an elevation of DNA synthesis also induced some morphological alterations in the bladder epithelium. The administration of AsA in conjunction with NaHCO3 or K2CO3 induced levels of change greater than those with either salt alone. In contrast, the degree of response in the bladder epithelium of rats given AsA-Na was reduced by the simultaneous administration of NH4Cl. These results suggest that the degree of DNA synthesis and/or morphological alteration in the rat-bladder epithelium after treatment with various bases may depend on changes in urinary concentrations of Na+ or K+ ions and/or pH, and the presence of ascorbic acid in the urine. The results are discussed in relation to the possible promotion by various treatment regimens (salts +/- AsA) of urinary bladder carcinogenesis.
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PMID:Participation of urinary Na+, K+, pH, and L-ascorbic acid in the proliferative response of the bladder epithelium after the oral administration of various salts and/or ascorbic acid to rats. 279 70

Several carriers mediate ionic fluxes across the plasma membrane in a variety of mammalian cell types. Intracellular proton concentration is regulated by virtue of the operation of at least two distinct systems: a stilbene-sensitive, Na+- dependent HCO3-/Cl- exchange system, and an amiloride-sensitive Na+/H+ antiporter. The contribution of these two transporters to the modulation of intracellular pH in response to either extracellular pH variations or cell stimulation by growth factors and tumor promoters has been studied in several cell lines, including fibroblast mutants lacking Na+/H+ antiport activity. The attainment of a permissive intracellular pH value is critical to the development of the mitogenic response elicited by growth factors. Kinetic studies have revealed particular features of the Na+/H+ antiporter that explain its function in the early sequence of biochemical events leading to DNA replication. The detailed investigation of the mechanisms by which protons and other ions might regulate cell proliferation has important implications for the understanding of the role of pH microenvironment in carcinogenesis, tumor development and chemotherapy.
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PMID:The Na+:H+ antiport in cancer. 302 4

The carcinogen N-acetoxy-N-2-acetylaminofluorene reacts with dG and dG-containing nucleotides to give good yields of the C-8 adducts, but the analogous 4-aminobiphenyl derivative does not. Replacement of the N-acetoxy group by 2,6-dichlorobenzoyloxy circumvents this difficulty. This reaction is shown to be generally applicable, and biphenylamido adducts with dG, d(CpG), d(GpC) and d(ApG) have been prepared. A new, useful deacetylation procedure employing the heterogeneous system sodium carbonate/methanol which leads to the corresponding biphenylamino derivative without appreciable imidazole ring opening is also reported.
Carcinogenesis 1988 Oct
PMID:A new synthetic route to nucleotide adducts derived from N-acetylated and unacetylated 4-aminobiphenyl. 316 60

The effects of magnesium carbonate (MgCarb) on carcinogenesis and natural killer (NK) cell modulation by nickel subsulfide (Ni3S2) were studied. Male Fischer F344/NCr rats, 50-90 g body wt, 20 rats per group, received single i.m. injections into both thigh muscles of 2.5 mg Ni3S2 alone or combined with different proportions of MgCarb; the Mg/Ni molar ratio ranged from 0.25 to 4.0. Control rats received i.m. injections of normal saline or magnesium acetate (MgAcet), or s.c. MgCarb at a site distant from Ni3S2. The animals were observed over 79 weeks for the development of tumors. The NK cell activity was determined over the first 3 weeks of the experiment in separate groups of rats treated as above, with the use of the 51Cr/YAC-1 release assay for blood and spleen cells and the peroxidase localization of Ox-8-immunoreactive lymphocytes at the injection site. I.m. administration of MgCarb mixed with Ni3S2 up to the Mg/Ni molar ratio of 1.0 inhibited the carcinogenicity of Ni3S2 in a dose-related manner; final incidence of sarcomas decreased from 100 to 55% and the appearance of first tumors was delayed from 25 to 39 weeks. Higher doses of MgCarb did not exert further effect. Distant s.c. injection of MgCarb or local i.m. application of MgAcet did not change the carcinogenic potency of i.m. Ni3S2. MgCarb or saline alone did not produce any tumors. I.m. Ni3S2 had no significant influence on the activity of NK cells in blood and spleen, while i.m. MgCarb alone did not affect the NK activity in blood but doubled it transiently in the spleen 24 h after injection. In the injected muscle, Ox-8-positive cells became abundant around MgCarb but could not be found close to Ni3S2. This inhibitory effect of Ni3S2 was partially reversed by MgCarb. Also, numerous multinucleated giant cells infiltrated the sites of injection of MgCarb alone and MgCarb + Ni3S2 but not Ni3S2 alone. The results indicate a dose-dependent and strictly local character of the inhibition by MgCarb of Ni3S2 carcinogenesis, as well as a possible involvement of NK and phagocytic cells in this inhibition.
Carcinogenesis 1987 Jul
PMID:Nickel--magnesium interactions in carcinogenesis: dose effects and involvement of natural killer cells. 359 18

This investigation was based on an epidemiologic association of milk consumption and decreased intestinal cancer risk. Furthermore, there is also some indirect evidence that calcium supplementation in humans and animals may decrease colon cancer risk and that calcium, by inference, may be the protective factor in milk. In order to investigate these associations in a controlled laboratory setting, dietary supplementation of low fat dried milk (37 g/kg diet; N = 18) and calcium carbonate (40 mg/kg rat/day; N = 17) were compared separately to regular diet controls in the rat-dimethylhydrazine colon carcinogenesis model. The results of this investigation showed that neither milk-supplemented rats nor calcium carbonate-supplemented rats had fewer DMH-induced colorectal (P = .374) or total gastrointestinal tumors (P = .291) than did regular diet controls (N = 10; by analysis of variance [ANOVA]). Milk supplementation did result in a significant decrease in tumor burden when measured by incidence of metastases (P = .035) and of intestinal obstruction (P = .011; by chi-square test), when compared with calcium-supplemented and control rats. Though this implies that milk supplementation provides protection against some aspects of carcinogenesis of the colon, in rats fed low fat diets, this does not appear to be mediated through the calcium content of milk.
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PMID:The effect of dietary milk and calcium on experimental colorectal carcinogenesis. 369 Dec 67


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