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)

Dietary administration of dehydroepiandrosterone (DHEA) (0.6%) or butylated hydroxytoluene (BHT) (1%) during or subsequent to two i.p. injections of azaserine (30 mg/kg body wt) resulted in significant alteration of yield of preneoplastic lesions in both pancreas and liver. While concomitant application appeared not to have any effect on subsequent development of glutathione S-transferase P form (GST-P) positive hepatocellular lesions in either case, BHT and to a lesser extent also DHEA reduced initiation of pancreatic acinar carcinogenesis. Both BHT and DHEA were associated with significant increase in GST-A form positive pancreatic foci when administered after cessation of carcinogen treatment while clearly inhibiting liver lesion development. The results point to a marked differential in the response of the liver and pancreas to external stimulus with regard to preneoplastic focal lesions while demonstrating significant second stage promotion of pancreatic acinar carcinogenesis by BHT and DHEA.
Carcinogenesis 1989 Feb
PMID:Modifying influence of dehydroepiandrosterone or butylated hydroxytoluene treatment on initiation and development stages of azaserine-induced acinar pancreatic preneoplastic lesions in the rat. 252 62

A rat liver gap junction (GJ) cDNA probe that detects mRNA encoding the 32 Kd GJ-protein (connexin 32) was employed to study GJ-protein gene expression in rat liver tumors induced by a single exposure to diethylnitrosamine (DEN) followed by exposure to 2-acetylaminofluorene (AAF)/CCl4/AAF or induced by systemic administration of N-ethyl-N-hydroxyethylnitrosamine (EHEN). All carcinomas generated by these carcinogens showed markedly reduced levels of GJ-protein mRNA. This may indicate that GJ-protein levels and gap-junctional intercellular communication (GJIC) capacity are also severely compromised. Moreover, all hyperplastic nodules also showed a reduced level of GJ-protein mRNA. Taken together with our earlier finding that the liver tumor promoter phenobarbital inhibits GJ-protein gene expression, these results suggest that deranged GJIC is a relatively early event in liver multistage carcinogenesis. A range of other cDNA probes was also used to characterize gene expression in the DEN-induced tumors. Induction of expression was seen for glutathione S-transferase (placental form) (GST-P), gamma-glutamyltranspeptidase (GGT), and c-raf but not for c-Ha-ras or c-myc.
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PMID:Changes in gap junction protein (connexin 32) gene expression during rat liver carcinogenesis. 255 87

The reversible stage of tumor promotion, which follows the stage of initiation and precedes that of progression in multistage carcinogenesis, is a unique example of reversible toxicity in biological systems. In order to study the molecular mechanisms involved in the action of promoting agents during this stage, the regulation of the expression of genes for two enzymes of glutathione metabolism, gamma-glutamyl transpeptidase (GGT) and the placental isozyme of glutathione S-transferase (GST-P), was studied under several different conditions of promotion during multistage hepatocarcinogenesis in the rat. Promotion by phenobarbital caused an increased expression of both of these genes in altered hepatic focal lesions, although this was somewhat more variable in the case of the GGT gene. C.I. Solvent Yellow 14, an industrial dye, served as an effective promoting agent. Feeding this dye resulted in a dramatic increase in the expression of GST-P, but not that of GGT in altered hepatic foci. Factors in crude, cereal-based diets inhibited the stage of promotion by diethylnitrosamine, but enhanced promotion by phenobarbital in a synergistic manner. In contrast, at least one purified diet had the converse effect during this stage. The mRNA levels of GST-P were uniformly elevated dramatically in reversible nodules and neoplasms of rat liver that had been induced by diethylnitrosamine and phenobarbital promotion. In contrast, the level of GGT mRNA was somewhat variable, with an occasional neoplasm exhibiting almost a background level of expression of this gene. Therefore, the altered regulation of multiple genes in hepatocytes during the stage of promotion can vary with the promoting agent itself; this process may be related to the heterogeneous gene expression seen in hepatic neoplasms. A possible role for specific DNA sequences in the 5' flanking regions of such genes is considered. In addition, a cDNA clone to the mRNA of human liver GGT was isolated and sequenced. The homology of the coding sequence of the human liver GGT mRNA to that of rat kidney GGT mRNA was striking.
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PMID:Regulation of the expression of some genes for enzymes of glutathione metabolism in hepatotoxicity and hepatocarcinogenesis. 256 99

Expression of the human placental form of glutathione S-transferase (GST-pi), an enzyme proposed as a marker for human and experimental neoplasia, was immunohistochemically evaluated in 51 samples of 'normal' and diseased adult human uterine cervix. Five fetal uteri were also studied. GST-pi positivity was detected in 54, 92, 95 and 83% of the 'normal', non-neoplastic, cervical intra-epithelial neoplasia (CIN) and cancer cases respectively. All five fetal uteri and the positive 'normal' adult cases presented cells immunostained for GST-pi throughout the thickness of the mucosa, including the basal layer. Some non-neoplastic conditions like inflammation, repair and metaplasia and some dysplastic and neoplastic lesions showed areas of positively stained cells within an otherwise negative tissue, indicating a phenotypic heterogeneity regarding the enzyme expression. Our results confirm that GST-pi has a fetal character and indicate that it may appear in the adult cervical squamous epithelia under 'normal' or pathological conditions not necessarily linked to the process of carcinogenesis. Therefore it cannot be used as a marker for cervical epithelial neoplasia.
Carcinogenesis 1989 Dec
PMID:Placental form of glutathione S-transferase in normal and diseased human uterine cervical mucosa. 259 Oct 20

In order to evaluate the role of the placental form of glutathione S-transferase (GST-Pi) as a tumour marker, activity and composition of GSTs from human colon were investigated. GSTs were purified from normal colon mucosa and from colonic tumours by affinity chromatography on glutathione-agarose. After SDS-PAGE or isoelectric focusing these purified preparations revealed only one band that comigrated with GST-Pi from human placenta. A monoclonal antibody (mAb) very specific for GST-Pi was developed and characterized. On immunoblot this mAb stains purified GST from normal and diseased colon tissue. GST activity was significantly higher in most cancerous (247 +/- 38 nmol/min/mg protein; n = 7), compared with the corresponding normal tissues (171 +/- 18 nmol/min/mg protein; n = 7). In colon from patients without large bowel malignancies GST-Pi is also by far the most prominent isoform detectable. In conclusion, both normal and tumorous colon tissue predominantly express GST-Pi and therefore GST-Pi is not suitable as a tumour marker for colonic carcinomas. However, the increased GST-Pi levels in colonic tumours could possibly contribute to the relatively high resistance to anti-cancer drugs.
Carcinogenesis 1989 Dec
PMID:Glutathione S-transferases in normal and cancerous human colon tissue. 259 Oct 27

The effect of clofibrate (CF) on proliferation of diethylnitrosamine (DEN)-initiated glutathione S-transferase placental form (GST-P)-positive preneoplastic and neoplastic lesions as studied in male F344 rats. Animals were given a single i.p. injection of 200 mg/kg body weight of DEN, and then from 2 weeks later were given a diet containing 0.3% CF (group 1), or no supplement (group 2) until week 64. Group 3 received an injection of 0.9% NaCl instead of DEN and then a diet containing 0.3% CF, like group 1. Animals in all groups were subjected to partial hepatectomy at week 3 and killed at weeks 8, 20, 32, 49 or 64. The results showed that development of GST-P-positive lesions was significantly less in group 1 than in group 2 from week 8 (P less than 0.05). However, in group 1, morphologically distinguishable GST-P-negative preneoplastic lesions increased from week 20 (P less than 0.05), and the total number of GST-P-positive and -negative lesions was significantly greater than that in group 2 from week 32 (P less than 0.05). The induction of hepatocellular carcinoma (HCC) was greater in group 1 than in group 2 from week 49. All the HCCs induced in group 2 were GST-P-positive, whereas 38.9% (7/18) of those in group 1 were GST-P-negative. In group 3, only a few GST-P-positive and/or -negative preneoplastic lesions developed by week 64. These results suggest that CF has tumor-promoting activity, and that GST-P-positive cells induced by DEN changed to GST-P-negative cells on subsequent treatment with CF.
Carcinogenesis 1989 Dec
PMID:Modulation of diethylnitrosamine-initiated placental glutathione S-transferase positive preneoplastic and neoplastic lesions by clofibrate, a hepatic peroxisome proliferator. 268 52

The effects of dietary Brussels sprouts and indole-3-carbinol (I3C) on xenobiotic-metabolizing enzyme activities and hepatic aflatoxin B1 (AFB1)-DNA binding were determined in rats. Animals were dosed intraperitoneally (i.p.) or intragastrically (i.g.) with [3H]AFB1 and killed 2 (i.p.) or 3 (i.g.) h later. Brussels sprouts caused a significant (P less than 0.01) 50-60% decrease in hepatic AFB1-DNA binding, and increased hepatic and intestinal glutathione S-transferase (GST) activities. Hepatic mono-oxygenase (AHH and ECD) activities were not altered in sprouts-fed rats, but greater than 2-fold increases in intestinal AHH and ECD activities were found. Although I3C increased intestinal AHH and ECD activities similarly to Brussels sprouts, I3C did not significantly decrease AFB1 binding, nor did it increase hepatic or intestinal GST activity. Route of administration did not alter the percentage inhibition of binding in comparison to control rats in either treatment group, suggesting that the small intestine may not play a significant role in the metabolism of AFB1. In a second experiment, rats were dosed either i.p. or i.g. with [3H]AFB1 and killed 2, 6, 12, 24 or 48 h later. Hepatic AFB1-DNA binding and tissue radioactivity levels were determined. Brussels sprouts once again significantly (P less than 0.001) decreased hepatic AFB1-DNA binding. Route of administration of the carcinogen did not affect DNA binding over time in sprouts-fed animals, confirming our previous results.
Carcinogenesis 1989 Apr
PMID:Effect of diet and route of administration on the DNA binding of aflatoxin B1 in the rat. 270 10

The single cells positive for placental glutathione S-transferase (GST-P), detectable in livers of rats soon after treatment with hepatocarcinogens, are possible 'initiated cells', the hypothesis tested in the present series of experiments. No low dose threshold was observed in male Sprague-Dawley rats at different single doses of diethylnitrosamine (DEN) although a plateau was reached between 160 and 200 mg/kg body weight. At the latter single dose approximately 12,400 positive cells/cm3 were observed immunohistochemically in rat livers after one week, the numbers then decreasing to week 8 and thereafter rising again. In the early stages single cells predominated but with time a gradual increase in mini-foci and larger lesions became evident. Application of selection pressure (feeding of diet containing 0.02% 2-AAF plus partial hepatectomy) to rats 2-24 weeks after single DEN-treatment resulted in the formation of large foci positive for GST-P, especially in the early stages, the growth response being less pronounced with time. The number of foci, on the other hand, was correlated with the number of single cells/mini-foci detected in hepatectomy tissue of the same individuals. These results suggest that the early GST-P positive populations could be the precursor for preneoplastic foci and nodules.
Carcinogenesis 1989 Nov
PMID:Transient induction of single GST-P positive hepatocytes by DEN. 280 31

A glutathione S-transferase (GST) isoenzyme having common antigenicity to rat placental form (GST-P) and human placental form (GST-pi) has recently been suggested may be a marker of carcinogenesis. In the present study we have investigated the expression of this isoenzyme in three small cell lung cancer cell lines in order to determine whether or not this isoenzyme can be used as a general marker of carcinogenesis. GST activity towards 1-chloro-2,4-dinitrobenzene in two of the cell lines (NES and NOC-361) was moderately higher than that in normal human lung, but this activity was markedly suppressed in one of the cell lines (NCI-H69). Quantitation of the GST isoenzymes in the tumors grown in nude mice by injecting these cell lines also revealed a moderate increase of GST-pi-type isoenzyme in NES and NOC-361 and its suppression in NCI-H69. Immunocytochemical localization studies with these tumors using antibodies raised against GST-pi also indicated a drastic decrease of GST-pi-type isoenzyme in NCI-H69 and this finding was confirmed by Western blot studies. These results suggest that GST-pi, or the isoenzyme(s) having similar immunological nature to GST-pi, cannot be used as the general markers of neoplastic states.
Carcinogenesis 1988 Jan
PMID:Expression of glutathione S-transferase isoenzymes in human small cell lung cancer cell lines. 282 36

Expression of glutathione S-transferase placental form (GST-pi) in human lung carcinoma tissue taken at autopsy or biopsy was investigated immunohistochemically. All of 34 cases of squamous cell carcinomas, including poorly, moderately and well-differentiated examples were shown to stain positively for GST-pi. Poorly differentiated adenocarcinomas were, however, negatively stained (0/5 cases), while moderately and well differentiated adenocarcinomas were found to stain with GST-pi at rates of 69% (9/13 cases) and 71% (5/7 cases), respectively. Six cases of small cell carcinomas examined were all negative. The results indicate that GST-pi may be a useful marker for non-small cell type lung cancer, especially squamous cell carcinoma which is in agreement with findings for rat lung neoplastic lesions reported previously.
Carcinogenesis 1988 Dec
PMID:Expression of the glutathione S-transferase placental form in human lung carcinomas. 284 80


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