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

Genetic trace metal disturbances can be at three levels. Trace metals play an important role in the metabolism of genetic macromolecules and the information transfer system. Deficiency or excess of trace metals caused either by dietary or genetic factors will affect the normal functioning of the whole organism. The roles of trace metals in carcinogenesis/mutagenesis and ageing are typical of this category. The second level of genetic trace metal disturbances affect the metabolic pathway of the trace metal itself. Biochemical derangement resulting from genetic defects cause aberrant metabolism of the element and thus disease symptoms. Diseases caused by abnormal metabolism of copper, zinc, iron, and molybdenum are discussed. Trace metal disturbances can also be the result of other genetic diseases. This aspect of genetic trace metal disturbances is least investigated. However, information should be important for improving the existing treatment protocol for the more common inborn errors of metabolism, such as phenylketonuria.
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PMID:Genetic trace metal disturbances. 258 Aug 76

The excess incidence of lung cancers observed in metallic mines other than iron mines probably can be correlated not only to radioactivity, but also to dust pollution. The present work investigates the role of surface properties of sulfides and arsenides, which are present in metal mines, in oxidizing mechanisms capable of inducing oxidative stress and, possibly, of participating in carcinogenesis. Using added spin-trapping agent followed by ESR spectroscopy, it was observed that nickel and copper arsenides can be very active in the oxidation of formate or DMSO, by reducing the oxygen dissolved in a cell-free medium. Sulfides, on the other hand, are not active, except for the iron sulfides, which are very active as an air-aged powder. The process of activation and rendering the particle surface passive was investigated. Surface dissolution and moderate grinding were found to be activating factors, while air-aging generally rendered the particle surface passive. The critical factor in determining activity is the availability of reducing species of iron, copper, or nickel on the surface of the minerals.
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PMID:Production of free radicals arising from the surface activity of minerals and oxygen. Part II. Arsenides, sulfides, and sulfoarsenides of iron, nickel, and copper. 262 58

About 35% (10-70%) of all cancers may be associated with nutritional causes (1). However, while natural or added substances in foods may be carcinogenic, nutritional deficiencies or excesses may promote carcinogenesis. We compared data from blacks and whites using dietary and nutritional status surveys in the United States to determine whether the poorer dietary patterns and nutritional status of American blacks may be associated with their higher incidence and mortality from certain cancers (compared with whites). Our review indicates that blacks eat more nitrate and animal foods and not enough fiber in relation to protein, fat, and carbohydrate. Blacks also have poorer nutritional status with respect to getting enough thiamine, riboflavin, vitamins A and C, and iron, to being obese (females), and to being underweight (males). This is in agreement with hypotheses regarding the interactions between diet and cancer (associations found in whites) and dose-response relationships reported for some cancers for which blacks have a higher incidence and mortality than whites. More large-scale prospective case-control and cohort studies are needed in both blacks and whites to elucidate the contribution of specific dietary and nutritional factors to the risk of specific cancers in these population groups. However, such studies must be preceded by methodological research to obtain more valid measures of dietary and nutritional status.
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PMID:Diet, nutritional status, and cancer risk in American blacks. 265 94

The radiomimetic agent hydrogen peroxide is known to produce DNA strand breaks, chromosome damage and cell death. It has also been identified as one of the cytotoxic agents formed during certain drug metabolism and by phagocytic cells in the respiratory burst. Our laboratory recently identified the ultimate reactive species responsible for the DNA-damaging and cytotoxic effect of H2O2 as being hydroxyl radical. This was achieved by the use of the specific iron chelator o-phenanthroline, which prevents the occurrence of a Fenton reaction between H2O2 and chromatin bound ferrous ions. In this paper we show that H2O2 is able to induce mutation at the HGPRT locus in V79 cells and morphological transformation of C3H/10T1/2 cells. o-Phenanthroline abolishes both effects, indicating that hydroxyl radical is directly involved in mutation and carcinogenesis.
Carcinogenesis 1989 Jun
PMID:o-phenanthroline protects mammalian cells from hydrogen peroxide-induced gene mutation and morphological transformation. 272 Aug 99

Dietary fibers may tend to enhance or inhibit chemically induced experimental colon cancer, depending on the particular fiber consumed. This study examined the relationship between colonic thymidine kinase enzyme activity and mucin histochemistry and the reported effects of various dietary fibers on chemically induced colon carcinogenesis. Fiber-supplemented diets containing fibers reported to inhibit (wheat bran) or enhance (guar gum, carrageenan) chemically induced colon carcinogenesis in the rat were selected. Four groups of male Fischer 344 rats consumed 10% wheat bran, 5% guar gum, 5% carrageenan, or fiber-free diets ad libitum for 4 weeks. At the completion of the treatment period, the distal 12 cm of colonic mucosa was scraped off and homogenized for determination of thymidine kinase activity, and a 0.5-cm section of midcolon was processed by the high-iron diamine/Alcian blue method for mucin histochemistry. Final animal weights did not differ significantly among groups. Thymidine kinase enzyme specific activity (mumole thymidine phosphate formed x 10(6)/min/mg protein, means +/- SEMs) was not significantly different in the fiber-free, wheat bran, and guar gum groups (10.98 +/- 1.50, 7.41 +/- 1.09, and 9.11 +/- 2.04, respectively) but was markedly elevated at 41.84 +/- 4.65 in the carrageenan group (alpha less than 0.001). Mucin histochemistry failed to reveal any significant differences among dietary groups.
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PMID:Alterations in colonic thymidine kinase enzyme activity induced by consumption of various dietary fibers. 284 79

The growth of C6 glioma and L1210 leukemic cells has been stimulated in serum-free medium by the addition or iron or transferrin. The growth promoting action of transferrin was lost when iron was chelated in the culture medium using desferrioxamine. L1210 cells can be grown continuously in serum-free medium supplemented with transferrin or FeCl3 only. In this latter case, it has been shown that L1210 cells secrete into the medium some factor which facilitates iron uptake. The growth of L1210 cells in their exponential phase was blocked by desferrioxamine at the G1-S interface of the cell cycle. The action of transferrin on cell growth was also inhibited by propyl gallate - a known antioxidant which prevents lipid peroxidation. The action of iron was more potent than hemin in reversing the influence of propyl gallate on L1210 cell growth. Iron was found to activate purified guanylate cyclase in the presence of unsaturated fatty acids. This suggests that cyclic GMP synthesis could be involved in the promotion of transformed cell growth by iron.
Carcinogenesis 1985 Mar
PMID:Growth promotion of transformed cells by iron in serum-free culture. 285 72

Newborn Swiss-Webster mice were given an intraperitoneal injection of 25 micrograms of dimethylnitrosamine. At weaning they began receiving 0.05% phenobarbital in the drinking water to promote the lesions for the term of the study. Preneoplastic foci and hyperplastic nodules were identified histologically by two markers, resistance to exogenous iron accumulation and an increase in gamma-glutamyltranspeptidase activity. AT 8, 12, and 16 weeks of age, livers of affected male mice exhibited 12, 18, and 12 iron-resistant foci/cm2 and 13, 9, and 9 gamma-glutamyltranspeptidase-positive foci/cm2, respectively (average for median right and right anterior sublobes). Iron-resistant nodules were first observed at 8 weeks; however, gamma-glutamyltranspeptidase-positive nodules were not noted until 12 weeks. In animals that received dimethylnitrosamine but were not placed on phenobarbital, there was an average of 5 foci/cm2 (iron-resistant or gamma-glutamyltranspeptidase-positive) at 12 weeks while no nodules were noted. This model could provide a practical short-term in vivo tool for the detection of early sequential cellular alterations produced by initiators, inhibitors, and promoters of carcinogenesis.
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PMID:Characterization of dimethylnitrosamine-induced focal and nodular lesions in the livers of newborn mice. 286 66

We have investigated the protective effects of S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR2721) on the induction by radiation of altered hepatocyte foci in 150-day-old Sprague-Dawley rats. WR2721 (100 micrograms/g of body weight) was administered to selected groups of neonatal animals 30 min prior to the administration of single doses of ionizing radiation (150 or 300 rads). Two focus phenotypes, described by the histochemical markers gamma-glutamyltranspeptidase and iron exclusion, were quantitated through the use of serial frozen sectioning techniques and computer-assisted image analysis. Although radiation was capable of inducing foci, induction was much more effective in female than in male rats. WR2721, however, reduced the frequencies of radiation-induced foci at both radiation doses, with the protective effect more readily apparent in female animals. The modulation of foci formation by WR2721 in the neonatal rat system suggests that this compound and related aminothiols may be useful probes for examining mechanisms of mutagenesis and carcinogenesis induced by radiation or chemicals.
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PMID:Protective effect of S-2-(3-aminopropylamino)ethylphosphorothioic acid against induction of altered hepatocyte foci in rats treated once with gamma-radiation within one day after birth. 286 3

To investigate mechanisms underlying the formation of carcinogen-induced altered hepatocyte foci, we histochemically examined the livers of 150-day-old rats that had been treated neonatally with single doses of gamma radiation (75, 150 or 300 rad, whole body) and i.p.-injected diethylnitrosamine (DEN, 0.15 mumol/g body wt) either separately or in combination. Three focus phenotypes, showing the elevated gamma-glutamyl transpeptidase [GG(+)] and/or the iron-exclusion [Fe(-)] histochemical marker(s) were quantitated through the use of serial frozen sectioning techniques and computer-assisted image analysis. DEN and gamma radiation each induced foci when given separately but total focus yield per cm3 of liver was more than 10-fold greater in DEN-treated than in irradiated rats and approximately 3-fold higher in females than in males. Combining the DEN and radiation treatments synergistically increased total focus yields for both sexes, although this response declined with increasing radiation dosage. For rats receiving DEN alone, the sex-dependent differential in total focus yield was due to the higher frequencies in females of the iron-excluding phenotypes [Fe(-) alone and Fe(-) + GG(+)]; the frequencies of foci showing only GG(+) were similar in both sexes. In contrast, the enhancement in total focus yield resulting from the combined DEN--radiation treatments was primarily a consequence of increases in the foci with GG(+) alone. The results suggest that (a) qualitatively different types of genetic damage (carcinogen-induced point mutations and radiation-induced rearrangements) may interact synergistically in the induction of phenotypically altered cells and (b) separate genetic loci are involved in the sex-mediated modulation of focus production and the synergistic enhancement of focus production by DEN--gamma radiation interactions.
Carcinogenesis 1986 Mar
PMID:Synergistic induction of altered hepatocyte foci by combined gamma radiation and diethylnitrosamine administered to neonatal rats. 286 9

The effect of butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) on the carcinogenicity in rats of aflatoxin B1 (AFB1) was investigated. AFB1 was administered by gastric intubation to male F344 rats at 25 micrograms/kg body wt three times a week such that a total dose of 1.5 mg/kg (0.48 mmol/kg) body wt was given over a period of 20 weeks and diets containing either 1000 or 6000 p.p.m. BHA or BHT were fed starting one more week before carcinogen, during administration and for one week after cessation. Animals were killed during exposure and at intervals up to 24 weeks after cessation. Liver altered foci and neoplasms were quantified using the exclusion of cellular iron after iron-loading and gamma-glutamyl transpeptidase reaction, as well as conventional staining for identification. Exposure to AFB1 alone induced substantial numbers of altered foci after 20 weeks, and at 24 weeks after cessation of exposure, the incidence of hepatocellular neoplasms was 63%. In the groups receiving BHA or BHT together with AFB1, the numbers of altered foci were decreased at all time points and at termination, the final incidence of liver cell neoplasms and number of neoplasms per animal were also reduced in a dose-related manner. Neoplasms in other organs were rare and were not affected by antioxidant treatment, except for a possible reduction of colon cancer. Thus, BHA and BHT inhibited the hepatocarcinogenesis of concurrently administered AFB1 without shifting the organotropism.
Carcinogenesis 1986 Jul
PMID:Dose-related inhibition of aflatoxin B1 induced hepatocarcinogenesis by the phenolic antioxidants, butylated hydroxyanisole and butylated hydroxytoluene. 287 75


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