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)

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

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

The literature on the occurrence of carcinogenesis as related to vitamin B6 deficiency is reviewed, and several critical areas, such as altered tryptophan metabolism, impaired immune status, and the metabolism of polyamines are discussed in depth. Preliminary results of vitamin B6-related chemotherapy of malignant melanomas are also presented.
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PMID:Vitamin B6 deficiency and carcinogenesis. 359 26

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) or 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), which is a potent mutagen from pyrolysates of tryptophan, was given subcutaneously to neonatal ICR mice, and all animals were observed for 1 year. Tumors of the livers and lymphoreticular tissue were induced. In the mice given Trp-P-1, the incidences of these tumors were as follows: liver tumors in 45% of the males; malignant lymphoma in 13% of the males and in 24% of the females. In the mice given Trp-P-2, the incidences of liver tumors in the males were dose-dependent (12.5 mg/kg, 12%; 25 mg/kg, 18%), while those of malignant lymphoma varied within a range from 5 to 19%. Statistical analysis revealed that the incidences of the liver tumor in the mice given Trp-P-1 or Trp-P-2 and those of lymphoma in the mice given Trp-P-1 were significantly higher than those of the controls. In the control mice, the incidences of tumors were as follows: malignant lymphoma in 5% of the females; lung tumor in 14% of both sexes.
Carcinogenesis 1987 Nov
PMID:Tumor induction in mice administered neonatally with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole or 3-amino-1-methyl-5H-pyrido[4,3-b]indole. 366 65

Portacaval anastomoses were performed in the rat to study urothelial carcinogenesis in this model and the promoting effect of dietary tryptophan. We were unable to produce any urothelial cancers or premalignant changes; some animals formed uric acid stones and developed papillary hyperplasia in the bladder. We conclude that the initiating carcinogen is likely to be exogenous and may be dietary in those experiments that have produced urothelial cancers.
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PMID:Urothelial carcinogenesis and portocaval anastomosis in the rat. 367 66


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