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

The modifying effect of four dose levels of butylated hydroxytoluene (BHT) on liver and bladder carcinogenesis by N-2-fluorenylacetamide (FAA) was studied in rats. FAA (200 ppm) was fed simultaneously with four levels of BHT (300, 1000, 3000, and 6000 ppm) to male F344 Fischer strain rats. Groups of animals were killed at 6, 12, 18, and 25 weeks. Hepatocellular-altered foci in the liver were identified histochemically by the exclusion of cellular iron after iron loading and by reaction for gamma-glutamyltranspeptidase. FAA alone induced altered hepatocellular foci which increased in number with duration of exposure, and by 25 weeks of feeding, 100% of rats had liver neoplasms. Concurrent feeding of BHT produced a dose-dependent reduction in the numbers of altered foci and the areas of liver sections occupied by histochemically altered cells, as well as a reduction in the incidence of liver neoplasms and the number of neoplasms per animal. These findings indicate that reduction of the number of foci at an early stage is predictive of reduced incidence of neoplasms at a late stage. Thus, BHT inhibited in a dose-dependent manner the hepatocarcinogenesis of concurrently fed FAA. However, although no bladder neoplasms occurred in rats given either BHT or FAA alone, groups fed BHT and FAA together developed bladder neoplasms in proportion to the dose of BHT. The effect of BHT on both liver and bladder carcinogenesis could be explained by BHT causing an alteration of the metabolism of FAA in the liver, resulting in less activation and greater urinary excretion of carcinogenic metabolites. In addition, BHT at high dose levels may exert a promoting effect on bladder carcinogenesis. Accordingly, it is suggested that the chemopreventive effect of phenolic antioxidants should be investigated with attention to the possibility that they not only inhibit carcinogenesis in the main target organs but also modify carcinogenesis in other organs.
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PMID:Dose-dependent reduction of N-2-fluorenylacetamide-induced liver cancer and enhancement of bladder cancer in rats by butylated hydroxytoluene. 670 70

Nitrite was formed on incubation of N-nitrosamines with a reconstituted monooxygenase system, consisting of cytochrome P-450 (P-450) and NADPH P-450 reductase from pig liver. Nitrite was not obtained when the nitrosamines were incubated with NADPH P-450 reductase alone or when molecular oxygen or NADPH were omitted. Interaction of nitrosamines with the reconstituted P-450 system or with hemoglobin under reducing conditions resulted in optical spectra identical with those obtained with nitrite. It is proposed that N-nitrosamines are denitrosated by electron transfer from the hemoprotein iron to the nitrosamine molecule.
Carcinogenesis 1982
PMID:Metabolic nitrite formation from N-nitrosamines: evidence for a cytochrome P-450 dependent reaction. 680 75

Mutagenicity in the urine of workers occupationally exposed to mineral oils and iron oxide particles and age matched workers only exposed to mineral oils was investigated using the Salmonella/mammalian microsome assay. Both groups of workers included smokers and non-smokers. Mutagenicity was significantly higher in the group of workers exposed to both mineral oils and iron oxide particles, the statistical significance of the difference being similar to that found when total non-smokers were compared with total smokers irrespective of occupational exposure. When only non-smokers of both groups of workers were compared, the extent of mutagenicity in the urine of workers exposed to iron oxide particles was still significantly higher, suggesting that smoking did not exhibit a significant enhancing effect on urinary mutagenicity of workers exposed to mineral oils and iron oxide particles, but instead seemed to enhance urinary mutagenicity similarly in both groups of workers. Whether or not this conclusion can be drawn may depend, among other factors, on the variability of the Ames assay. To cope with this particular problem, the possible usefulness of a mutagenicity factor is discussed.
Carcinogenesis 1982
PMID:Urinary mutagenicity in occupational exposure to mineral oils and iron oxide particles. 713 65

Epidemiological evidence proves conclusively that lung cancer correlates with air pollution. However, data on lung cancer death rates and smoking show that mankind accepts the risk of long-term and low-level exposure to carcinogens. As a rule, immediate benefits are sought and remote hazards ignored. Fear of atmospheric contamination by radioactive fallout seems to be the main factor for awareness of air pollution. Experimental works help us to understand physics of particle deposition in the lungs (inertial impactation, sedimentation, Brownian movement), shed light on carcinogenesis (eg, bay region theory in case of polycyclic aromatic hydrocarbons and surface charge changes regarding asbestos), show that atmospheric particulates accepted as harmless may act as co-carcinogens (eg, iron and benzo(a)pyrene) and stress the importance of in vitro researches (bacterial mutation tests, organ cultures, sister chromatid exchange system) to screen pollutants for their malignant potential and study their pathogenesis.
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PMID:Air pollution and lung cancer. 718 64

The frequency of low nutrient intakes was investigated in areas of moderate and high oesophageal cancer incidence in Transkei by means of 24-hour recall and habitual intake studies in children and nursing mothers. The results in moderate- and high-risk regions were similar and habitual intakes of protein, energy, phosphorus, iron, thiamine and vitamin A were generally satisfactory. Intakes of less than two-thirds the Recommended Dietary Allowances (RDA) had a high frequency of inadequate intakes for calcium (90%), nicotinic acid (79%), riboflavin (55%) and ascorbic acid (50%). It is concluded that the possibility of long-standing deficiencies of the latter three vitamins playing a role in oesophageal carcinogenesis should be considered.
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PMID:Nutrient intakes among rural Transkeians at risk for oesophageal cancer. 733 Jul 40

The fluorescence yield of benzo[a]pyrene (BP) increases dramatically upon its transfer from the surface of particulates to rat liver microsomes. Adsorption of BP to Canadian chrysotile, anthophyllite, hematite and silica results in greatly enhanced uptake rates into microsomes when compared to uptake from a microcrystalline dispersion of BP. The fibrous minerals chrysotile and anthophyllite were more effective than silica and hematite in enhancing BP uptake. Simple mixtures of BP microcrystals and particles did not display enhanced transport, indicating that adsorption of BP to the particulate surface is necessary for enhanced microsomal uptake. BP was not released into microsomes from carbon black. We suggest that particulate-enhanced availability of BP may be of significance in the co-carcinogenesis between particulates and polynuclear aromatic hydrocarbons. However, other mechanisms are also possible, and are not excluded by our experiments. The fluorescence methodology, described in this paper provides a novel and convenient means to quantify microsomal uptake of BP and thereby investigate further the mechanisms of cocarcinogenesis.
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PMID:Benzo[a]pyrene uptake into rat liver microsomes: effects of adsorption of benzo[a]pyrene to asbestos and non-fibrous mineral particulates. 735 28

Iron is excluded from foci of hepatocellular alteration in carcinogenesis of rodents and some fish. Among white perch (Morone americana), there is a condition of hepatic copper storage in which copper-loaded livers are produced naturally. In a group of fish collected from the Chesapeake Bay, Maryland (USA), from September to December 1990, we observed hepatic lesions which excluded copper similar to the phenomenon of iron exclusion, in a white perch with over 3,600 micrograms/g wet weight hepatic copper. The lesions were of two types: one with cells morphologically different from normal hepatocytes and which had diminished to absolute exclusion of copper with the copper specific histochemical stain rubeinic acid, and a second with cells morphologically similar to normal hepatocytes which had only a partial exclusion of copper. Although the exact cause and nature of the lesions was not determined, intrinsic copper toxicity, environmental pollution, or a combination of these factors may have contributed to their development.
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PMID:Exclusion of copper from altered hepatocytes in white perch (Morone americana) with hepatic copper storage. 756 36

The induction of hepatocarcinogenesis by polychlorinated biphenyls (PCBs) in C57BL/10ScSn mice is markedly potentiated by iron. To investigate the effects of iron and PCBs on nuclear populations, C57BL/10ScSn mice received a single dose of iron-dextran (600 mg Fe/kg) and were fed a diet containing 0.01% of the PCBs mixture Aroclor 1254 for up to 6 months. DNA content of isolated nuclei and hepatocytes was estimated by flow cytometry. Cell suspensions and nuclei isolated from Aroclor treated mice after 6 months contained increased diploid (2N) populations compared to controls. In contrast, iron treatment of mice markedly enhanced fractions of octoploid (8N) nuclei by 2 weeks and this effect persisted over the 6 month period. When Aroclor 1254 and iron were administered together there was a synergistic increase in the mononucleated diploid fraction which was significant at 2 weeks and highly significant at 6 months. This became the predominant nuclear effect. At six months, Aroclor 1254 and iron, both alone and in combination, also increased the rate of DNA synthesis in hepatocytes as measured by bromodeoxyuridine (BrdU) incorporation. The chronic polyploidizing effect of iron overload alone was investigated further and shown to be proportional to the dose and was detectable as early as 2 days after 600 mg Fe/kg and 1 week after 150 mg Fe/kg. Polyploidization of nuclei was inhibited by the oral iron chelator CP94. Iron also induced a prolonged reduction in the incidence of binucleated cells. Histologically, nuclear enlargement due to iron was confined to the midzonal region of the liver lobule, whereas iron deposition was greatest in the periportal region. Iron (600 mg/kg) also caused increased nuclear polyploid states in hepatocytes of adult rats and gerbils. Similarly, weanling mice with a dominantly diploid cell population, when treated with iron (300 mg/kg), exhibited a significant shift to a tetraploid (4N) population and a marked increase in proliferation as measured by BrdU incorporation and proliferative cell nuclear antigen (PCNA) detection. These results indicate that Aroclor 1254 and iron induce changes in the mouse hepatocyte population that involve 2N and 8N nuclei respectively. The combination treatment leads to the emergence and proliferation of a mononucleated, diploid population as observed frequently in chemical hepato-carcinogenesis. The reason for the chronic polyploidizing effect of iron is unknown, but may imply both increased DNA synthesis and impairment of nuclear division with implications in human conditions of iron overload.
Carcinogenesis 1995 Apr
PMID:Perturbation of hepatocyte nuclear populations induced by iron and polychlorinated biphenyls in C57BL/10ScSn mice during carcinogenesis. 772 49

The early cellular events in liver carcinogenesis were studied in Fischer-344 male rats that either were fed 200 ppm 2-acetylaminofluorene (AAF) for up to 10 wk or were fed the carcinogen for 8 wk followed by maintenance for an additional 24 wk. By 1 wk of exposure, AAF caused a reduction in the number of glutamine synthetase (GS)-positive centrilobular hepatocytes, an increase in DNA synthesizing hepatocytes in the central areas of the hepatic lobules, and a shift from multinucleated to mononucleated hepatocytes, although overt hepatocellular necrosis was not evident. By 3 wk, altered hepatocellular foci characterized by deficiencies in iron storage (IS-) and collagen production and by expression of gamma-glutamyl transferase (GGT+) and placental-type glutathione transferase (PGT+) activity appeared. Single PGT+ cells were also found. During continued exposure, foci increased in number, size, and total area with the increases escalating between 8 and 10 wk of exposure. Cessation of AAF exposure at 8 wk resulted in a slight decrease in the number of foci after a further 6 wk of maintenance, but with continued maintenance for another 6 and 12 wk, the number again increased. IS- characterized the majority of foci during carcinogen administration, whereas after cessation of exposure, GGT+ and PGT+ foci predominated. None of the foci were positive for GS. After AAF exposure for 10 wk, a few neoplasms developed and greater numbers occurred after maintenance for a further 24 wk of rats exposed for 8 wk. We conclude the following: (a) the low dose of AAF caused subtle alterations in function and proliferation of normal hepatocytes and converted hepatocytes into focus cells; (b) reduction of the GS+ area is a sensitive indicator of cytotoxicity of AAF; (c) the development of some foci at an early stage depends on a promoting action of AAF, which ceased when the carcinogen was withdrawn, allowing some foci to undergo reversion; (d) a strong linkage exists in expression of IS-, GGT+, and PGT+ in foci; (e) the carcinogenic process accelerates in the absence of any indication of increased cytotoxicity by AAF; and (f) under the conditions of this study, no GS+ foci, adenomas, and carcinomas were found, indicating that no carcinogen-induced expression of GS occurred in these lesions and that GS expression is not linked to other phenotypic abnormalities.
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PMID:Sequential functional and morphological alterations during hepatocarcinogenesis induced in rats by feeding of a low dose of 2-acetylaminofluorene. 773 79

Chinese hamster V79 cells were transfected with human transferrin receptor cDNA, lacking the 3' untranslatable regulatory sequence. One of the clones obtained was investigated completely. It exhibited the cDNA sequences recombined into the genome, transcribed the corresponding mRNA and became partially constitutive in iron uptake from transferrin. The rate of iron uptake was significantly higher in these cells than in the parental ones, as was the intracellular iron content, assessed indirectly by measuring the activation of the regulatory protein responsible for iron homeostasis control. The transfected cells were more sensitive to the DNA-damaging action of H2O2. This corroborates the important role that iron plays as a mediator of DNA damage by reactive oxygen species. It also points to the possibility that mutations at the regulatory sequences of transferrin receptors, leading to partial disturbance in iron homeostasis, might render the cells more prone to further mutations and malignant transformations by reactive oxygen species.
Carcinogenesis 1995 Jun
PMID:Cells transfected with transferrin receptor cDNA lacking the iron regulatory domain become more sensitive to the DNA-damaging action of oxidative stress. 778 51


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