Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male F344 rats were administered phenobarbital, polychlorinated biphenyl (PCB), retinol acetate, indomethacin, 6-amino-caproic acid, dexamethasone (DEX) or diethylmaleate (DEM) for one week and then were treated with these chemicals plus butylated hydroxyanisole (BHA) for a further four weeks. Histopathologically, the incidence of BHA-induced forestomach hyperplasia was significantly lower in rats treated with PCB, DEX or DEM than in those treated with BHA alone. However, the inhibition by PCB and DEX was only partial and might have been due to decreased food intake. On the other hand, DEM completely inhibited the hyperplastic response to BHA at a dose of 0.25%, and even at lower doses it demonstrated significant inhibition without any decrease in body weight or food intake. The result that DEM, a tissue glutathione depleting agent, can inhibit BHA-associated forestomach hyperplasia strongly suggests that tissue glutathione may be intimately involved in the induction of forestomach hyperplasia by the antioxidant in rats.
Carcinogenesis 1987 Oct
PMID:Effects of simultaneous treatment with various chemicals on BHA-induced development of rat forestomach hyperplasia--complete inhibition by diethylmaleate in a 5-week feeding study. 311 20

The effects of retinol and retinoic acid on cytotoxicity and mutation expression at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster ovary (CHO) cells with or without exogenous metabolic activation were studied in the presence and absence of known chemical mutagens. Neither retinol nor retinoic acid induced mutants at the HGPRT locus of CHO cells at concentrations ranging from 1 microM to 50 microM without exogenous metabolic activation, and at concentrations ranging from 1 microM to 25 microM in the presence of Aroclor 1254-induced rat liver S9. Retinol and retinoic acid did not affect 100 micrograms/ml ethyl methanesulfonate-induced cytotoxicity or mutations at the HGPRT locus of CHO cells in the absence of exogenous metabolic activation at concentrations ranging from 1 microM to 25 microM. In contrast, retinol and retinoic acid inhibited 7,12-dimethylbenz[a]anthracene-induced cytotoxicity and mutation induction at the HGPRT locus of CHO cells when either uninduced Sprague-Dawley rat liver S9, Aroclor 1254-induced Sprague-Dawley rat liver S9 or co-cultivated primary Sprague-Dawley rat hepatocytes were used to provide metabolic activation. These data show that retinoids are capable of inhibiting mutation induction in mammalian cells in vitro by a chemical promutagen requiring metabolic activation to a reactive form, and suggest that such inhibition is due to an alteration of mutagen metabolism.
Carcinogenesis 1988 Jul
PMID:Inhibition of 7,12-dimethylbenz[a]anthracene-induced genotoxicity in Chinese hamster ovary cells by retinol and retinoic acid. 313 30

In order to elucidate the mechanism of tumor prevention of beta-carotene, its effect on sister chromatid exchanges (SCE) induced by MNNG in cultured V79 cells, under condition free of the enzyme system to convert beta-carotene into vitamin A, was studied. It was found that SCE level was significantly increased by high doses beta-carotene (10(-5)-10(-4) M) and the enhancement of SCE was restored to its original level by addition of alpha-tocopherol (final concentration 2 micrograms/ml). This may be due to the latter inhibiting the oxidation of beta-carotene and reducing the amount of oxidated carotene, which is toxic for cultured cells. Combination of beta-carotene and alpha-tocopherol at low doses inhibited SCE induced by MNNG (P less than 0.05) but no protective activity was observed when used separately. It was also found that beta-carotene (2 x 10(-7) M) and retinol (16 micrograms/ml) inhibited SCE induced by aflatoxin B1, which is activated by S-9 mixture. The present data clearly show that the antitumor activity of beta-carotene may be attributed to both itself and its degraded compound vitamin A, and may take part in the initiation of carcinogenesis. Combination of beta-carotene and other cancer preventive drugs is more effective and safer than it used individually.
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PMID:[Effect of beta-carotene on sister chromatid exchanges induced by MNNG and aflatoxin B1 in V79 cells]. 314 77

Ornithine decarboxylase (ODC, EC 4.1.1.17) activity was measured, without exogenous stimulation, in the liver, oesophagus and lung of Wistar rats which were vitamin A deficient or supplemented with retinol or retinoic acid. The enzyme basal activity in such deficiency conditions was higher, when compared with controls, in the oesophagus and especially in the lungs. Retinoic acid normalized enzyme activity only at high doses (300 micrograms/day). In the liver, initial retinol deficiency did not sensitively modify ODC activity, and retinoic acid then stimulated the enzyme abnormally. This phenomenon could not be observed at later stages of vitamin deficiency (but there again without cytological abnormalities or thymidine incorporation disturbances): liver ODC response then became comparable to that of other tissues. These results highlight the particular basal hyperactivity of pulmonary ODC during the initial stages of vitamin A deficiency, indicative of an enhanced tendency to cell proliferation. A special stimulating effect of retinoic acid on ODC, contemporary with early deficiency, was observed in the liver; this effect was not observed at a later stage in normally fed rats.
Carcinogenesis 1988 Dec
PMID:Ornithine decarboxylase basal activity in liver, oesophagus and lung of vitamin A deficient rats, and the effect of retinoic acid. 319 61

The preventive and therapeutic potential of selenium (Se), a micronutrient, against cancer has been well documented in several test systems, but the mechanism of its action is not known. The possibility that Se might function in a manner similar to steroid hormones and retinoids through mediation of cellular receptors was examined. A specific 2S cellular binding protein (SeBP) for Na2[75Se]O3 was detected in rat tissue extracts. Liver and intestine exhibited highest levels of SeBP, and heart, uterus and spleen had the lowest levels. Oral administration of Na2[75Se]O3 to rats resulted in its uptake by the tissues with concomitant appearance of [75Se]SeBP complex. The protein binds sodium selenite with moderately high affinity; the apparent dissociation constant was determined by Scatchard analysis to be 1.1 X 10(-7) M. SeBP focused at pH 5.3 upon isoelectric focusing in ampholines of pH 3-10. Competitive binding affinity studies with unlabeled test compounds revealed that selenium dioxide and selenocystine showed high binding affinity (90-95%) for the selenite-binding site on SeBP. Sodium selenate, elemental Se powder, and selenomethionine, however, showed poor competition with sodium selenite. Biological activity of the above selenocompounds, as expressed by others, correlate with their binding affinities for SeBP. Sodium sulfite showed 35% inhibition of Na2[75Se]O3 binding, but sulfate showed none. Two ultimate carcinogens, N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine, and two retinoids, retinol and retinoic acid, showed less than 10% inhibition of binding. Interaction of Se with SeBP is completely blocked by thiol inhibitors. Plasma transport of Na2[75Se]O3 is mediated by a protein with a mol. wt of 68,000, which is presently identified, by immunoprecipitation studies as well as by Affi-Gel Blue column chromatographic experiments, as serum albumin. The results suggest that the plasma transport of Se is facilitated by albumin, and that the intracellular transport of Se for its biological functions is accomplished by SeBP.
Carcinogenesis 1988 Feb
PMID:Specific binding proteins for selenium in rat tissues. 333 11

The dye-coupled intercellular communication across gap junctions in primary hamster tracheal epithelial cells has been studied in serum-free, hormone-supplemented medium. In the absence of vitamin A, non-cytotoxic concentrations of cigarette-smoke condensate (CSC) inhibited intercellular communication between tracheal epithelial cells in a concentration-dependent way. All-trans retinol and retinoic acid showed biphasic effects on intercellular communication depending on their concentration. Physiological concentrations of retinol and retinoic acid increased the dye-coupled transfer of Lucifer Yellow CH via gap junctions compared with the dimethylsulfoxide-treated tracheal epithelial cells. At pharmacological concentrations retinol slightly increased the intercellular communication in the first 2 h of the exposure period, whereas upon longer treatment times with retinol and retinoic acid, gap-junction-mediated intercellular communication was inhibited almost completely. When retinol was given to tracheal epithelial cells before exposure to CSC or simultaneously with CSC-exposure, retinol counteracted the inhibitory potential of CSC on intercellular communication. The results of the present study clearly indicate that both CSC and all-trans retinol influence the intercellular communication between primary hamster tracheal epithelial cells in serum-free, hormone-supplemented culture medium.
Carcinogenesis 1988 Feb
PMID:Effect of retinol and cigarette-smoke condensate on dye-coupled intercellular communication between hamster tracheal epithelial cells. 333 16

The risk of invasive and intraepithelial cervical neoplasia in relation to the frequency of intake of the major sources of preformed vitamin A (retinol) and beta-carotene in the Italian diet was analyzed in a study of 392 cases of invasive cancer compared with 392 age-matched controls hospitalized for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer, and of 247 cases of cervical intraepithelial neoplasia compared with 247 controls found to have normal smears at the same screening clinics where cases had been identified. Women with invasive cancer consumed milk, green vegetables, and carrots less frequently, but no significant relation was noted for meat or liver. Consequently, estimated beta-carotene, but not retinol, intake was inversely and strongly related to the risk of invasive cervical cancer. Compared with women whose intake was over 150,000 international units (IU) per month, the relative risks were 3.0 for 100 to 149,999 and 4.7 for less than 100,000 IU. It was not possible to show that these relationships were incidental, since allowance for several identified potential distorting factors, including indicators of social status and the major risk factors for cervical cancer, did not materially modify the risk estimates. In contrast, no association emerged between any of the food items and vitamin A estimates considered and intraepithelial neoplasia. Thus, the results of this study can be interpreted in one of two ways: either some residual uncontrolled bias was responsible for the strong dietary correlates of invasive cervical cancer risk or beta-carotene (or any other correlate of a vegetable-rich diet) has effect on one of the later stages of the process of carcinogenesis, thus influencing the risk of invasive carcinoma but not of its precursors.
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PMID:Dietary vitamin A and the risk of intraepithelial and invasive cervical neoplasia. 337 43

Several vitamin compounds have been tested for their ability to suppress the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine, a direct acting mutagen/carcinogen, in Salmonella typhimurium strain TA100. Menadione, alpha-tocopherol, retinal and retinol have displayed high inhibitory activity. The antimutagenic activity of menadione, in particular, has been found to be remarkable in as much as less than equimolar amount can reduce the mutagenic potency of the carcinogen by 50%. In vitro data suggest that its action is mediated by accelerating the deactivation of the N-nitroso carcinogen, possibly involving the formation of a quinone radical.
Carcinogenesis 1988 Aug
PMID:Modifying role of vitamins on the mutagenic action of N-methyl-N'-nitro-N-nitrosoguanidine. 340 49

Both beta-carotene (beta-C), a vitamin A precursor, and vitamin A itself have been shown to reversibly inhibit neoplastic transformation in 10T1/2 cells during the progression phase of carcinogenesis. In order to determine whether the activity of beta-C in these cells may be attributed to conversion to vitamin A or is intrinsic to the carotenoid molecule, the uptake and metabolism of beta-C, and of retinal, the immediate product of dioxygenase-cleavage of beta-C, was studied in 10T1/2 cells. Cellular uptake of 2.6 nmol/10(6) cells occurred 24 h after treatment with 10(-5) M beta-C. Thereafter, cell levels remained relatively stable between 1 and 2 nmol/10(6) cells over the 1-week treatment period. Upon removal of beta-C from the medium, cellular levels decreased by approximately 80% in 2 weeks, then stabilized. Retinal was rapidly and quantitatively converted to retinol by 10T1/2 cells, suggesting that the inhibitory action of retinal on neoplastic transformation in these cells is due to its conversion to retinol, and that any enzymatic conversion of beta-C to retinal by these cells would be expected to result in retinol as the end product. Using [14C]beta-C, we found no evidence for formation of [14C]retinol, [14C]retinal or [14C]retinoic acid using sensitive HPLC. We therefore conclude that beta-C has intrinsic chemopreventive activity in 10T1/2 cells, perhaps due to its anti-oxidant properties.
Carcinogenesis 1988 Sep
PMID:Uptake and metabolism of beta-carotene and retinal by C3H/10T1/2 cells. 340 59

The effect of mild vitamin A deficiency or vitamin A supplementation on methylbenzylnitrosamine (MBN; CAS: 937-40-6)-induced esophageal carcinogenesis was examined in Sprague-Dawley rats. The animals were fed semipurified diets containing levels of retinyl acetate, which were adequate (2.2 mg/kg diet), deficient (0.30 mg/kg diet), or supplemented (29.9 mg/kg diet) with respect to vitamin A content. Carcinogen-treated rats received 2.5 mg MBN/kg (body wt) twice a week for 5 weeks; they were then sacrificed for evaluation of esophageal tumorigenesis 15 weeks later. Liver levels of retinol reflected vitamin A nutriture, but there were no clinical signs of deficiency or toxicity. There were no significant differences in the frequency or incidence of esophageal tumors (either carcinomas or papillomas) among the dietary groups. There was also no indication that either vitamin A deficiency or vitamin A supplementation influenced the formation of preneoplastic lesions. Although the time was short for the neoplastic development, tumors were observed. These data suggest that vitamin A is selective in tissues it may protect from cancer induction and that the esophagus is less involved than other tissues.
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PMID:Effect of vitamin A nutriture on experimental esophageal carcinogenesis. 347 42


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