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

The possibility that alpha-tocopherol (vitamin E) inhibits the formation of nitrosomorpholine (NMOR) in vivo was investigated in mice orally pretreated with alpha-tocopherol (2.5-100 mg/kg body wt) once daily for 6 days. Twenty-four hours later, the animals were injected i.p. with 2 mg of morpholine (MOR) per animal followed by exposure to 47 p.p.m. of NO2 for 2 h. Under these conditions, low oral doses of alpha-tocopherol (2.5-5 mg/kg body wt) significantly decreased NMOR formation in vivo. As total body alpha-tocopherol levels increased, in vivo NMOR formation decreased, and a maximal 50-70% inhibition of NMOR formation occurred at alpha-tocopherol levels of 5 micrograms/g body wt. Additional results showed that NMOR was rapidly eliminated in mice, so that studies which measure the levels of NMOR found in animals treated with MOR and then exposed to NO2 may underestimate the amount of NMOR that is actually formed. Finally, oral pretreatment of up to 100 mg of alpha-tocopherol/kg body wt had no effect on NMOR elimination.
Carcinogenesis 1986 Mar
PMID:Inhibitory effect of alpha-tocopherol on the formation of nitrosomorpholine in mice treated with morpholine and exposed to nitrogen dioxide. 394 20

A single exposure to a low concentration (10(-10) mol/l) of tumor promoters [such as 12-O-tetradecanoylphorbol-13-acetate (TPA), phenobarbital and nafenopin] or hormones [such as epidermal growth factor (EGF), glucagon and insulin] or drugs [such as imidazole and indomethacin] stimulated the 24-h flow into DNA synthesis and mitosis of primary neonatal rat hepatocytes incubated in high-calcium (1.8 mmol/l) Eagle's FBS(10% v/v)-MEM. However, only tumor promoters acted as enhancers of hepatocytic DNA synthesis when a low-calcium (0.01 mmol/l) FBS-MEM was used. The activity of tumor promoters was totally suppressed by the simultaneous (or nearly such) addition of low doses (from 25.0 to 0.25 micrograms/ml; activity, from 100 to 0.7 U/ml) of exogenous bovine liver and ox and dog erythrocyte superoxide dismutase (SOD), independent of the calcium concentration of the medium. Even at the minimal dose administered, SOD effectively inhibited the stimulatory actions of TPA concentrations up to 10(-6) mol/l. SOD's blocking effect depended upon its enzymatic activity, as it was prevented by a specific inhibitor of SOD, sodium diethyldithiocarbamate (DDC). By contrast, SOD did not inhibit the growth stimulation elicited by hormones and drugs in hepatocytes maintained in high-calcium FBS-MEM. Moreover, several tumor promoters (namely TPA, phenobarbital, nafenopin, saccharin, teleocidin, benzoyl peroxide, BHT, DDT, lindane, clofibrate and melittin) stimulated DNA synthesis even when the hepatocytes were incubated in the serumless HiWoBa2000 medium, whatever its calcium concentration. In this synthetic medium, tumor promoters' stimulatory activity was again completely inhibited by the simultaneous administration of exogenous SOD. Known antioxidants such as retinoids, vitamin E, selenous acid, and 7,8-benzoflavone, when given simultaneously with TPA, also prevented the stimulation of hepatocytic growth. These results disclose the existence of two quite different mechanisms by which the growth of neonatal rat hepatocytes can be stimulated: (i) the physiological-pharmacological extracellular calcium-dependent SOD-insensitive system mediating the effects of EGF, glucagon, insulin, imidazole, and indomethacin; and (ii) the pathological extracellular calcium-independent SOD- and antioxidant-suppressible mechanism operated by agents belonging to the tumor promoters class and involving, as a critical step, the generation of superoxide anions on the surface of the hepatocyte plasmalemma.
Carcinogenesis 1984 Dec
PMID:Exogenous Cu,Zn-superoxide dismutase suppresses the stimulation of neonatal rat hepatocytes' growth by tumor promoters. 633 36

Skin carcinogenesis can be operationally and mechanistically divided into at least three stages; tumor initiation, stage I and stage II of promotion. Current information suggests that reactive intermediates of skin tumor initiators are mutagenic and bind convalently to DNA of epidermal stem cells (dark basal keratinocytes) leading to some irreversible alteration in the differentiation capacity of these cells. Inhibitors of skin tumor initiation by polycyclic aromatic hydrocarbons (PAH) decrease the level of the PAH diol-epoxide bound to specific DNA adducts. The tumor promoters have been shown to have many cellular and biochemical effects in the skin. Recent data suggests that free radicals may be important in skin tumor promotion. The first stage of promotion is partially irreversible and can be accomplished by a single treatment of a tumor promoter such as TPA or by non-promoting agents such as 4-0-methyl-TPA, calcium ionophore A23187, and hydrogen peroxide, as well as wounding. These agents increase the number of dark basal keratinocytes, which suggest that these cells are important in the first stage of promotion. Prostaglandin E2 was found to specifically enhance stage I of promotion whereas the protease inhibitor tosyl phenylalanine chloromethylketone (TPCK) specially inhibited stage I of promotion and the TPA-induced dark basal keratinocytes. The second stage of promotion is initially reversible but later becomes irreversible. The weak promoting agent mezerein is an effective stage II promoter. Polyamines and epidermal cell proliferation appear to be important events in stage II of promotion. Putrescine was found to specifically enhance stage II, whereas retinoic acid (RA), diflouromethylornithine (DFMO), and butylated hydroxyanisole (BHA) specially inhibited stage II of promotion and the mezerein-induced polyamine levels. Floucinolone acetonide (FA) was found to inhibit both stages but was more effective in counteracting stage I of promotion. Although, TPA can cause a decrease in the number of glucocorticoid receptors during promotion, FA can effectively prevent this loss. Recent data suggest that skin tumor promotion can be effectively inhibited by a combination of stage I and II inhibitors. Furthermore, skin carcinogenesis can be counteracted by a combination of low and nontoxic doses of BHA, TPCK, DFMO and vitamin E.
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PMID:Multistage skin carcinogenesis: a useful model for the study of the chemoprevention of cancer. 638 17

Forty-eight young male and female golden hamsters (Mesocricetus auratus) were divided into four groups of 12 animals each. The left buccal pouches of Group 1 and 2 animals were painted 3 times weekly with a 0.5% solution of 7,12-dimethylbenz(a)anthracene (DMBA) in heavy mineral oil for 7 weeks. At the end of this period, the left buccal pouches of Group 2 animals were painted 3 times weekly with vitamin E (DL-alpha-tocopherol, in pure form) for an additional 4 weeks. Group 3 animals were painted with vitamin E only, for 4 weeks. Group 4 animals were untreated controls. Group 2 animals demonstrated a significant delay in tumor formation in comparison with Group 1 animals. Gross observation revealed fewer and smaller tumors in the Group 2 animals; microscopic examination revealed smaller tumors with better cellular differentiation and less invasion. No tumors were observed in Group 3 and Group 4 animals. These observations were similar to those made in previous studies of oral carcinogenesis using systemic vitamin E to delay tumor formation.
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PMID:Retardation of experimental oral cancer by topical vitamin E. 644 34

Oxidative damage and the role of antioxidants and prooxidants in aerobic metabolism is of great current interest; it spans areas of research such as carcinogenesis, ageing, toxicology and nutrition. We have used Bantin-Kingman female rats for both in vivo and in vitro studies. In these animals we have altered the levels of all-rac-alpha-tocopherol (vitamin E) by dietary means and have used physical exercise and visible light exposure to alter oxidative stress. Our results show a progressive and specific increase in the susceptibility of many subcellular membranes to oxidative damage with increasing levels of vitamin E deficiency and/or physical stress. In addition, endurance training raised the levels of antioxidative enzymic pathways in both skeletal and cardiac muscle.
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PMID:Vitamin E, physical exercise and tissue oxidative damage. 655 8

The effect of the antioxidant vitamin E on the tumor-inducing ability of 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was investigated in randomly bred Swiss mice. Three groups of mice that were 6 weeks of age at the beginning of the experiment received the following treatments: a) vitamin E acetate [DL-alpha-tocopheryl acetate (TA)] at a 4% dose level in a powdered diet for life; b) 1,2-DMH, 10 weekly sc injections at 20 micrograms/g body weight; c) combination of a and b treatments. The administration of TA enhanced the tumorigenicity of 1,2-DMH, as evidenced by statistically significant incidences of tumors in the duodenum, cecum, colon, rectum, and anus. The present finding apparently is in contrast with the reported inhibitory effect of TA on colon carcinogenesis by 1,2-DMH.
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PMID:Enhancing effect of vitamin E on murine intestinal tumorigenesis by 1,2-dimethylhydrazine dihydrochloride. 657 81

Biochemical analyses were conducted to evaluate the nutritional status of a high esophageal cancer risk population in Linxian, People's Republic of China. A study was conducted in September 1980 in which plasma levels of vitamins A, B2, and C were analyzed. In a second study in 1983, the plasma fat-soluble vitamins were analyzed with a newly developed high-performance liquid chromatography method that allowed the simultaneous determination of retinol, alpha-tocopherol, beta-carotene, alpha-carotene, and lycopene in 0.1 ml of plasma sample. The average plasma retinol levels ranged from 24 to 27 micrograms/dl among the population groups, with 20-35% of the individuals having levels under 20 micrograms/dl. Low plasma beta-carotene levels averaging 8-12 micrograms/dl were observed among the population groups. Low plasma alpha-tocopherol levels with average values around 700 micrograms/dl were also observed; about half the individuals were either low or deficient in vitamin E. After 4 months of supplementation with daily multivitamin tablets, the plasma contents of retinol and alpha-tocopherol were significantly increased. The plasma alpha-carotene and beta-carotene were also increased, possibly as a reflection of seasonal changes in the diet or a sparing effect of vitamins A and E on these carotenes. Low plasma ascorbate levels with an average of 567 micrograms/dl were observed, and about 23% of the individuals had values under 200 micrograms/dl. Riboflavin deficiency was prevalent, with about 90% of the subjects having an erythrocyte glutathione activation coefficient over 1.2. The study establishes the low nutritional status in vitamins of the population in Linxian and provides the background for further studies on the effects of nutritional deficiency on carcinogenesis.
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PMID:Vitamin A and other deficiencies in Linxian, a high esophageal cancer incidence area in northern China. 659 53

In the Basel study (BS) (1960-73) on cardiovascular and peripheral arterial diseases, a mortality follow-up was completed for the period 1965-80. Of the 4,224 men at risk for these diseases, 531 died. The causes of death were established from the death certificates and classified into 8 groups. For each case 2 age- and sex-matched controls were selected and compared with the corresponding cases with regard to the various variables obtained at the three examinations (1960, 1965, 1971). This report dealth with cancer mortality, plasma lipids, plasma vitamins, alcohol and cigarette consumption, and intake of milk and citrus fruits. The results were all obtained at the second follow-up examination (BS III, 1971-73). Cancer of the lung, stomach, large bowel, and all other sites were treated separately. The average follow-up from BS III until death varied from 3.7 years (other sites) to 4.9 years (cancer of the lung). Of 129 cancer deaths, the highest incidence was found for cancer of the lung (38) followed by stomach (19) and large bowel, (15) and the remainder (57) was for other sites. Plasma lipids did not differ significantly among cases and controls. However, the lowest values were observed in colorectal cancer and gastric carcinoma (mean cholesterol, 213 mg/dl). beta-Carotene was significantly lower in cancer cases of the lung than in controls (14.8 micrograms/dl vs. 23.7; P less than .05). It was also low in gastric cancer cases (13.0 micrograms/dl). Vitamin A was below average only in cases with gastric cancer (difference due to the small number not significant). Vitamin C was consistently lower in cancer cases than in controls. The lowest value was found for cancer of the stomach and corresponded to a below-average consumption of citrus fruits. Vitamin E was low in cancer of the colon. Plasma lipids correlated strongly with vitamin E (tau = 0.5) and to a lesser extent with vitamin A (tau = 0.25). beta-Carotene correlated poorly with beta-lipoproteins (low-density and very low-density lipoproteins) but significantly with total cholesterol. Smoking was inversely related, as was alcohol consumption, to the beta-carotene level. From these results, the conclusion was that vitamins influence carcinogenesis in humans.
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PMID:Cancer, vitamins, and plasma lipids: prospective Basel study. 659 56

The antitumor effects of vitamin A and its related substances, vitamin E, vitamin K, beta-carotene, ubiquinone, phytol, and squalene, were examined using a syngeneic murine tumor system. Intraperitoneal administration of these substances (0.19 mumol/mouse/day) slightly suppressed the growth of Meth A fibrosarcoma cells inoculated s.c. into Balb/c mice. Administration of all test substances except beta-carotene significantly suppressed the growth of Meth A fibrosarcoma cells rechallenged in Meth A-primed mice on day 10, but did not influence the growth of Meth 1 fibrosarcoma cells (another syngeneic tumor of Balb/c origin) rechallenged in Meth A-primed mice on day 10. The growth of Meth A tumor cells was suppressed when Meth A was inoculated together with lymph node cells obtained from the Meth A-primed Balb/c mice treated with vitamin A, vitamin E, phytol, or squalene. Our findings suggest that certain constituents in green-yellow vegetables may contribute to the prevention of cancer by augmenting an immunological response against tumor cells in the early stages of carcinogenesis.
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PMID:Immunological role of vitamin A and its related substances in prevention of cancer. 666 79

The anaerobic reductive metabolism of the urinary tract carcinogen 2-amino-4-(5-nitro-2-furyl)-[2-14C]-thiazole ([14C]ANFT) was examined in vitro using rabbit liver and kidney microsomes. The intermediate(s) produced during the reduction binds to tRNA, DNA, and protein. ANFT reduction was inhibited by oxygen, required NADPH and was not inhibited by SKF-525A or allopurinol. No binding to tRNA or DNA was observed if the nucleic acids were added at the end of the incubation. The covalent binding of an ANFT metabolite(s) to nucleic acids and protein was inhibited by the antioxidants vitamin E and butylated hydroxytoluene. The stoichiometry of microsomal reduction shows 3 mol of NADPH were used/mol of ANFT reduced. In inner medullary microsomes, the apparent Km and Vmax were 0.05 mM and 0.92 nmol/mg/min, respectively. Two metabolites from the anaerobic incubation of ANFT were isolated. The metabolites were tentatively identified as 1-(2-amino-4-thiazolyl)-3-cyano-1-propanone and 2-amino-4-(5-hydroxyl-amino-2-furyl)thiazole.
Carcinogenesis 1982
PMID:Anaerobic metabolism and nuclear binding of the carcinogen 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT). 681 38


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