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)

A simple and efficient method for the purification of mutagenic heterocyclic amines from heated meat products has been developed. In only two steps, namely extraction of raw material on Kieselgur followed by medium pressure liquid chromatography on Sephasorb HP, very clean fractions with high recovery rates of mutagenic compounds were obtained, thus allowing isolation and quantitation by high performance liquid chromatography (HPLC) with UV detection. The method was validated on both food grade and bacterial beef extracts as well as fried beef. In 1-5 g samples of beef extracts, levels up to 70 p.p.b. (ng/g) of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), 8-90 p.p.b. of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and up to 8 p.p.b. of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) were determined. In fried beef, 1 p.p.b. of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 1 p.p.b. of MeIQx were measured. The quantitative results of beef samples were in agreement with results from determinations using immunoaffinity chromatography/HPLC or liquid chromatography coupled with mass spectrometry. MeIQx could be quantified in fried beef down to 1 ng/g of fresh beef material. According to assays performed with reference standards of tryptophan and glutamic acid pyrolysis products, the method could also be extended to quantitate other heterocyclic amines.
Carcinogenesis 1989 Jul
PMID:An efficient and convenient method for the purification of mutagenic heterocyclic amines in heated meat products. 266 Oct 43

Rutaecarpine alkaloids have the capacity to inhibit specific 2,3,7,8-[1,6-3H]tetrachlorodibenzo-p-dioxin (TCDD) binding in rat liver cytosol, as analysed by electrofocusing in polyacrylamide gel. The IC50 value for binding of 7,8-dehydrorutaecarpine was estimated to approximately 7 nM indicating a high-affinity interaction, whereas rutaecarpine appeared less active (IC50 approximately 110 nM). These findings are of interest in view of the fact that analogues to these compounds may be formed following UV-irradiation of tryptophan and that such photo-products have been suggested to constitute (the) endogenous ligand(s) for the TCDD receptor. As further support of this notion, the rutaecarpine alkaloids investigated could be fitted into a rectangle of 6.8 x 13.7 A, a characteristic common for most high affinity ligands of the TCDD receptor hitherto studied. In view of their structural similarity to dehydrorutaecarpine and the agreement of their mol. wt with that of the photoproduct with the highest affinity for the TCDD receptor, we suggest deaza-analogues of dehydrorutaecarpine to represent possible candidates for the endogenous TCDD receptor ligand.
Carcinogenesis 1989 Apr
PMID:Interactions of rutaecarpine alkaloids with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver. 270 13

X-ray-irradiated BALB/3T3 A31-1-1 cloned cells were post-treated with lithocholic acid (LCA), one of the bile acids, and 3-hydroxyanthranilic acid (3HOA), a tryptophan metabolite, in order to examine their potential to promote cell transformation. Insulin was added to the medium so as to increase the sensitivity of the cells to transformation. A dose-dependent increase in the number of transformed foci was observed with LCA. 3HOA had a very weak, though significant, activity. Transformation frequency was increased only a little, if any, by the treatment with cholic acid, which is structurally related to LCA. Anthranilic acid, an analogue of 3HOA, had no such effect. The results are discussed in view of the importance of endogenous promoters.
Carcinogenesis 1989 Sep
PMID:Promotional effect of lithocholic acid and 3-hydroxyanthranilic acid on transformation of X-ray-initiated BALB/3T3 cells. 276 58

The ingestion of an elevated level (2%) of L-tryptophan (TRP) in a purified diet was investigated to determine whether it would influence the induction of gamma-glutamyltranspeptidase (GGT)-positive foci in the livers of rats exposed to a hepatocarcinogen. Subtotal hepatectomies were performed, and 18 h later, the rats were given injections i.p. of diethylnitrosamine (30 mg/kg). Ten days later, groups of male rats were placed on choline-supplemented (CS), CS + TRP, choline-deficient (CD), or CD + TRP diets for 10 wk. In two separate experiments, the rats fed the CS + TRP diet or the CD diet developed more and larger GGT + foci than did rats fed the CS diet. Rats fed the CD + TRP diet revealed similar changes to those found in rats fed the CD diet. The liver weights of the rats fed the CD or the CD + TRP diet were greater than those of rats fed the CS or the CS + TRP diet. Hepatic GGT activity was somewhat elevated in rats fed the CS + TRP diet and markedly elevated in rats fed the CD or the CD + TRP diet. Hepatic ornithine decarboxylase activity was increased in rats fed the CD + TRP diet. The results suggest that increased dietary tryptophan has a promoting effect on liver carcinogenesis as measured by the induction of GGT + foci in the livers of rats exposed to diethylnitrosamine. A potentiating effect by tryptophan was not observed in the livers of rats fed a CD diet.
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PMID:Influence of dietary tryptophan on the induction of gamma-glutamyltranspeptidase-positive foci in the livers of rats treated with hepatocarcinogen. 286 88

The behaviour of rat liver putative preneoplastic lesions with respect to the enzyme tryptophan oxygenase (TO), a liver-specific differentiation marker, and a possible growth-related marker, glucose-6-phosphate dehydrogenase (G6PD) was investigated during and after their induction by diethylnitrosamine initiation and subsequent 'selection pressure'. Using specific antibodies to rat liver TO and G6PD and the avidin-biotin complex method for immunohistochemical staining it was demonstrated that all of the nodular lesions showing increased expression of G6PD during the induction phase were also negative or deficient in TO enzyme protein. With the onset of 'phenotypic instability' or loss of marker enzymes, a gradual return to normal expression of TO activity was evident. Administration of dexamethasone and L-tryptophan 11 weeks after cessation of carcinogen treatment allowed differentiation between morphologically altered, apparently persisting lesions in which no, or little, enzyme induction was apparent and instable lesions showing a strong increase in levels of TO protein. Thus, persisting nodular lesions share a common lack of response to normal homeostatic physiological control.
Carcinogenesis 1986 Aug
PMID:Immunohistochemically demonstrated suppressed expression of tryptophan oxygenase, a marker for liver differentiation, within putative preneoplastic rat liver lesions. 287 5

N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was given to male Fischer 344 rats at a dose of 0.05% in drinking water for 2, 4, 6 and 12 weeks, and double soft agar colony formation of the uroepithelial cells was determined periodically, during and after this administration. In the group administered BBN for 2 weeks, no significant colony growth was observed until week 8. In the group given BBN for 4 weeks, colony growth was observed at week 4 and the numbers of colonies remained constant until week 8. In the group given BBN for 6 weeks, significant colony growth was observed at weeks 6 and 8. In the group on BBN for 12 weeks, colonies grew from week 4 and significant numbers of colonies were observed from week 6, increasing up to week 10. Colony formation preceded papilloma development in the rat bladder, and was dependent on the duration of BBN administration. The effect of amino acids and sodium saccharin on colony formation was also evaluated. The rats were given 0.05% BBN for 3 weeks, followed immediately by the administration for 9 weeks of 2% L-tryptophan, 1% D-tryptophan, 2% L-leucine, 2% D-leucine, 2% DL-leucine, 2% L-isoleucine, 2% DL-isoleucine or 5% sodium saccharin in the diet. At week 12, the numbers of colonies were significantly higher in the groups given sodium saccharin, L-leucine, DL-leucine, L-isoleucine, DL-isoleucine and D-tryptophan. This method provides a potentially useful approach toward analyzing the early events in bladder carcinogenesis and may be applicable to detect new bladder carcinogens and promoters.
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PMID:Soft agar colony formation of bladder cells during carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine and application to detection of bladder cancer promoters. 311 59

Transcriptional activation of the int-1 gene by proviral insertion mutations is thought to be a key step in mammary tumor induction by the mouse mammary tumor virus (MMTV). To test this hypothesis, we have constructed an int-1 allele resembling those found in virus-induced tumors, with an MMTV LTR placed 5' to the int-1 gene in the opposite transcriptional orientation. Transgenic mice harboring this allele express int-1 RNA at high levels in mammary and salivary glands of male and female mice and in male reproductive organs. The mammary glands of males and virgin females are grossly hyperplastic compared with those of nontrasgenic littermates. Mammary and (less frequently) salivary adenocarcinomas occur in these animals at rates indicating that transcriptional activation of int-1 and associated hyperplasia are initiating events in multistep carcinogenesis.
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PMID:Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. 318 Feb 22

DBA/2, BALB/c or (BALB/c X DBA/2)F1 (CDF1) mice of both sexes were treated for 1 week with a dietary hepatocarcinogenic tryptophan pyrolysate component (Trp P-1 or Trp P-2), and the activity of hepatic microsomal enzyme(s) for mutagenic activations of Trp P-1 and Trp P-2 were assessed by means of a mutation test with Salmonella typhimurium TA98. In both Ah-responsive (BALB/c and CDF1) and Ah-nonresponsive (DBA/2) mice, the dietary treatment with Trp P-1 or Trp P-2 resulted in a significant increase of the enzyme activity for mutagenic activations of Trp P-1 and Trp P-2 in females but not in males, except the case of male BALB/c mice treated with dietary Trp P-1. Also induction of enzyme(s) in female mice was suppressed by an administration of testosterone. The induced hepatic microsomal enzyme(s) was demonstrated to be cytochrome P-450 isozyme(s) (mol. wt of 55,000 daltons) by immunoblots with use of an anti-rat cytochrome P-448 monoclonal antibody and by selective inhibition of the activity by addition of 7,8-benzoflavone into the mutation assay system. These findings indicate that carcinogenic aromatic amines such as Trp P-1 and Trp P-2 are able to induce hepatic cytochrome P-450 isozyme(s) not only in Ah-responsive mice (BALB/c and CDF1) but also in Ah-nonresponsive DBA/2 mice and that the cytochrome P-450 induction is controlled by androgen(s).
Carcinogenesis 1988 Apr
PMID:Hepatic cytochrome P-450 isozyme(s) induced by dietary carcinogenic aromatic amines preferentially in female mice of DBA/2 and other strains. 335 64

Results from in vivo and in vitro studies showing that antioxidants may act as anticarcinogens support the role of active oxygen in carcinogenesis and provide impetus for exploring the functions of dietary antioxidants in cancer prevention by using in vitro models. We examined the single and combined effects of selenium, a component of glutathione peroxidase, and vitamin E, a known antioxidant, on cell transformation induced in C3H/10T-1/2 cells by x-rays, benzo[a]pyrene, or tryptophan pyrolysate and on the levels of cellular scavenging systems and peroxide destruction. Incubation of C3H/10T-1/2 cells with 2.5 microM Na2SeO3 (selenium) or with 7 microM alpha-tocopherol succinate (vitamin E) 24 hr prior to exposure to x-rays or the chemical carcinogens resulted in an inhibition of transformation by each of the antioxidants with an additive-inhibitory action when the two nutrients were combined. Cellular pretreatment with selenium resulted in increased levels of cellular glutathione peroxidase, catalase, and nonprotein thiols (glutathione) and in an enhanced destruction of peroxide. Cells pretreated with vitamin E did not show these biochemical effects, and the combined pretreatment with vitamin E and selenium did not augment the effect of selenium on these parameters. The results support our earlier studies showing that free radical-mediated events play a role in radiation and chemically induced transformation. They indicate that selenium and vitamin E act alone and in additive fashion as radioprotecting and chemopreventing agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown while vitamin E appears to confer its protection by an alternate complementary mechanism.
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PMID:Selenium and vitamin E inhibit radiogenic and chemically induced transformation in vitro via different mechanisms. 345 98

This paper reviews some of the earlier experimental studies concerning the role that tryptophan plays in enhancing tumorigenesis induced by selected chemical carcinogens. For many years, tryptophan has been implicated in carcinogenesis of the bladder. The evidence regarding tryptophan's effect on hepatic tumorigenesis is conflicting; an enhancing effect has been reported by some investigators, but a reduction in tumorigenesis has been reported by other workers. Some of the unique effects that tryptophan exerts upon the liver are reviewed. Also, experimental studies from our laboratory are reported in which we observed a potentiating effect of increased dietary tryptophan on the induction of gamma-glutamyltranspeptidase-positive foci in liver when rats were fed a choline-supplemented diet but no potentiation was found when rats were fed a choline-deficient diet for 10 weeks. The results suggest that increased dietary tryptophan has a promoting effect on liver carcinogenesis as measured by the induction of gamma-glutamyltranspeptidase-positive foci in the livers of rats exposed to diethylnitrosamine. The possible significance of these findings is reviewed.
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PMID:Role of tryptophan in carcinogenesis. 359 19


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