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

Silicon carbide whiskers (SiCW) and continuous glass filaments are important components of composite materials having potentially widespread use in the automotive, aerospace, and power generation industries. We determined the in vitro activity of three well-characterized samples of silicon carbide whiskers and a continuous glass filament sample in four different cellular assays and compared this to the activities of UICC crocidolite, JM Code 100 glass microfiber, and erionite in the same assay systems. The SiCW had a diameter range of 0.32-0.75 microns and a length range of 4.5-20.1 microns. The SiCW was significantly toxic; on a mass basis, one SiCW sample was more toxic than crocidolite; however, JM Code 100 glass microfiber, which is not toxic in vivo (i.e., it does not cause fibrogenesis or carcinogenesis when inhaled), was also more toxic than crocidolite. The glass filament sample was the least cytotoxic of all the samples tested. On a fiber number basis, all three SiCW samples were more toxic than crocidolite. The results of our study showed that SiCW exhibits significant in vitro biological reactivity. Thus, despite the caution that must be exercised in extrpolating the results of in vitro studies to conclusions about in vivo health effects, SiCW should be considered toxic until further toxicological data are available.
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PMID:In vitro activity of silicon carbide whiskers in comparison to other industrial fibers using four cell culture systems. 132 Mar 27

High doses of sodium saccharin, a non-genotoxic chemical, lead to the formation of silicate-containing precipitate and microcrystals in urine of male rats. Differences in urinary protein, pH, sodium and other factors affect silicate-containing precipitate and microcrystal formation as well as the bladder effects of sodium saccharin. Total urinary silicon concentration (mostly soluble) in sodium saccharin-fed rats is similar to or lower than the concentration in control rats. Binding of saccharin to male rat urinary proteins was demonstrated by equilibrium-gel filtration. We propose that by binding to urinary proteins under appropriate conditions, saccharin produces a nidus for the formation of silicate-containing precipitate and crystals. These appear to be cytotoxic to the superficial bladder epithelium, with cell death resulting in regenerative hyperplasia. Factors that influence the formation of these silicate-containing materials might provide a rationale for sex, species, dose and dietary differences in response to sodium saccharin.
Carcinogenesis 1991 Sep
PMID:A proposed role for silicates and protein in the proliferative effects of saccharin on the male rat urothelium. 189 14

Almost from its discovery in 1879, the use of saccharin as an artificial, non-nutritive sweetener has been the center of several controversies regarding potential toxic effects, most recently focusing on the urinary bladder carcinogenicity of sodium saccharin in rats when fed at high doses in two-generation studies. No carcinogenic effect has been observed in mice, hamsters, or monkeys, and numerous epidemiological studies provide no clear or consistent evidence to support the assertion that sodium saccharin increases the risk of bladder cancer in the human population. Mechanism of action studies in the one susceptible species, the rat, continue to provide information useful in assessing potential risk to the human from saccharin consumption. Unlike typical carcinogens which interact with DNA, sodium saccharin is not genotoxic, but leads to an increase in cell proliferation of the urothelium, the only target tissue. It also appears that the effect of saccharin is modified by the salt form in which it is administered, despite equivalent concentrations of saccharin in the urine. The chemical form of saccharin in the urine is unaffected, and there is no evidence for a specific cell receptor for the saccharin molecule. Changes in several urinary parameters, such as pH, sodium, protein, silicates, volume, and others, appear to influence the reaction of the urothelium to sodium saccharin administration. Silicon-containing precipitate and/or crystals appear to be generated in the urine under specific circumstances, acting as microabrasive, cytotoxic material. Using a mathematical model of carcinogenesis, which encompasses the temporal dynamics and complexity of the process at a cellular level, including spontaneous genetic transitions, it has been shown that the effects of sodium saccharin can be explained entirely in terms of its non-genotoxic influence on cell proliferation. In interpreting these analytical studies in the human context, particularly as they pertain to the urinary milieu which appears to be pivotal in the effect of sodium saccharin, we are led to the conclusion that there is a threshold effect in male rats and that an effect on the human urothelium is unlikely at even the highest levels of human consumption.
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PMID:The health risks of saccharin revisited. 220 24

"Energetic" biological trace elements [gallium (III), germanium (IV), silicon (silica), arsenic (V) and selenium (IV)] occurring in DNA of eukaryotic cells may improve the semiconductor properties of DNA and may influence the mechanisms that control genetic expression at the electronic level. Their roles are postulated as follows: (i) to maintain the level and direction of free sliding electrons in DNA, (ii) to modulate the electron conductivity and hole conductivity of DNA. This specific electronic nature of DNA take the form of magnetic pigeonholes in which an electric pulse is (0), or is not (1) stored as an area of local magnetisation. These types of conductivity occurring in different parts of DNA of different cells could participate in the switch on and switch off of genetic information in gene expression. This model may help to elucidate the mechanism of action of these naturally occurring antitumor agents and may help in understanding the role of trace elements in charge transport of DNA and in carcinogenesis.
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PMID:Carcinogenesis as the result of the deficiency of some essential trace elements. 305 Mar 86

Silicon carbide is a widely used synthetic abrasive manufactured by heating silica and coke in electric furnaces at 2400 degrees C. Until recently it had been considered a relatively inert dust in humans and animals. However, several roentgenologic surveys had revealed lesions similar to low-grade silicosis. A recent epidemiological study has revealed a 35% incidence of pulmonary problems. Tissues from three such workers were available for light microscopy. A mixed pneumoconiosis was found, and lesions can be summarized as follows: (a) abundance of intraalveolar macrophages associated with a mixture of inhaled particles including carbon, silicon, pleomorphic crystals, silicon carbide, and ferruginous bodies showing a thin black central core; (b) nodular fibrosis, generally profuse, containing silica and ferruginous bodies and associated with large amount of carbon pigment; (c) interstitial fibrosis, less prominent than the nodular form; (d) carcinoma in two cases. We believe this pneumoconiosis is sufficiently characteristic to be recognized as a distinct entity. The Stanton hypothesis on fiber properties and carcinogenesis could be applied to silicon carbide dust. At present, it appears that the occupational hazard is limited to the manufacturing process and powdered product used in some industries.
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PMID:Pathology of silicon carbide pneumoconiosis. 323 93

Silica fibres derived from plants are common contaminants of human diet in certain regions of the world where oesophageal cancer reaches extremely high incidences. We show here that one of these types of fibre (derived from Phalaris canariensis L) promotes the occurrence of tumours in the skin of mice initiated with a polycyclic carcinogen. Three experiments are described. In the first, the grain which bears these fibres was added to the diet. This did not result in any abnormality in any part of the gastrointestinal tract, but there was a significant induction of tumours in the skin around the mouth and nose; these were the areas of the body surface which most frequently came into contact with the grain. In the second experiment, the mice were separated from the grain by an intervening wire gauze barrier; a similar number of tumours appeared on initiated mice treated in this way. In this case, contact now occurred most frequently on the dorsal surface, which was rubbed against the gauze barrier, and it was on this surface that the tumours appeared. No tumours appeared if the grain was removed. In the third experiment, pure fibres were isolated from the surface of the grain and boiled in strong nitric acid so as to remove any organic material. When these acid-cleaned fibres were applied to the initiated skin with light pressure, they promoted carcinogenesis in the same way as croton oil. In each experiment the majority of tumours produced were benign neoplasms, together with at least one squamous carcinoma. It seems possible that the size and shape of these fibres are the critical properties determining their promoting activity. Their mean diameter is 15 microns, their modal length close to 200 microns, and they are sharply pointed with a tip diameter of 0.5 micron.
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PMID:Biogenic silica fibre promotes carcinogenesis in mouse skin. 609 84

A total of 40 metals are reviewed and summarized to give a general perspective on the metal's two major effects, relevant to medicine and psychiatry in man. These two effects are metal excess (poisoning) and deficiency. These metals are grouped arbitrarily into six categories; (a) The heavy metals, (b) the essential and questionable essential trace elements, (c) the macrominerals, (d) the alkali metals, (e) elements used as therapeutic agents, and (f) miscellaneous elements. The heavy metals are invariably toxic and could be lethal, and no deficiency state has yet been described in man, although arsenic has been postulated to be essential. The essential trace elements are vital to a number of vital physiological and biochemical functions, and newer essential trace elements are to be identified in the future. The recent findings suggest vanadium excess may aggravate the affective symptoms in bipolar affective disorder; selenium may inhibit certain carcinogenesis such as oesophageal cancer; and silicon may inhibit atheromatous formation in the aorta. There is also some suggestion that certain allergic syndromes may be correlated with very low levels of iron, copper, manganese. The study of elements will undoubtedly expand the understanding of disease processes in medicine and psychiatry.
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PMID:A synopsis on metals in medicine and psychiatry. 652 32

At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies. 788 19

In recent years green tea has been shown to afford protection against chemical- and photo-carcinogenesis in several animal tumor bioassay systems. It has been suggested that the wide range of anticarcinogenic properties of green tea may be due to the antioxidant effect of epicatechins present therein. In this study, we assessed whether these epicatechin derivatives (ECDs)--namely (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin (EC) inhibit spontaneous and photo-enhanced lipid peroxidation (LPO) in mouse epidermal microsomes. Our data indicate that significant inhibition (significance levels for P, < 0.05 to < 0.0001) was evident by EGCG, EGC and ECG in Fe3+/ADP supported LPO. Interestingly each of these epicatechin derivatives was also effective in inhibiting photo-enhanced LPO generated by incubating epidermal microsomes in the presence of silicon phthalocyanine and 650 nm irradiation. However, at equimolar basis, EGCG, which is also the major constituent in GTP, showed maximum inhibitory effects compared to other ECDs. Taken together, our results provide the direct evidence for the antioxidant property of ECDs, and suggest that such an effect may contribute towards anticarcinogenic (specifically anti-skin tumor) promoting effects of green tea.
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PMID:Inhibition of spontaneous and photo-enhanced lipid peroxidation in mouse epidermal microsomes by epicatechin derivatives from green tea. 818 54

Scanning electron microscopy (SEM) has proven useful in various aspects of urinary bladder carcinogenesis research and these are reviewed as they pertain to our research involving sodium saccharin in the rat. Sodium saccharin-carcinogenesis in rats requires administration at high doses beginning at birth or earlier. Administration beginning at ages of 5 weeks or later results in much lower incidences of bladder tumors. Methods were developed for examining the rat fetal and neonatal bladder to further evaluate effects at these critical ages. Several significant differences were found by SEM between the fetal bladder compared to the adult. The typical polygonal superficial cells of the bladder with asymmetric unit membrane were present before birth, but the slow turnover rate of the adult bladder did not occur until 3-4 weeks of age. Sodium saccharin causes increased proliferation rates and hyperplasia of the urothelium which is dose-dependent. SEM was found to be more sensitive than either light microscopy or labeling indices to detect the earliest lesions induced by sodium saccharin. More recently, amorphous and crystalline material in the urine of rats fed high doses of sodium saccharin were detected by SEM examinations which contained silicon as well as calcium, phosphate, and magnesium as detected by energy dispersive X-ray analysis (EDS) with the SEM. These parameters may be relevant to differences between rats and humans and pertain to extrapolations regarding risk assessment.
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PMID:Application of scanning electron microscopy and X-ray analysis to urinary tract cancer in animals and humans. 831 5


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