Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Exposure to exogenous alkylating agents, particularly N-nitroso compounds, has been associated with increased incidence of primary human brain tumors, while intrinsic risk factors are currently unknown. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a major defense against the carcinogenicity of N-nitroso compounds and other alkylators. We report here that in 55% (64/117) of cases, histologically normal brain tissue adjacent to primary human brain tumors lacked detectable MGMT activity [methyl excision repair-defective (Mer-) status]. The incidence of Mer- status in normal brain tissue from brain tumor patients was age-dependent, increasing from 21% in children 0.25-19 years of age to 75% in adults over 50. In contrast, Mer- status was found in 12% (5/43) of normal brain specimens from patients operated for conditions other than primary brain tumors and was not age-dependent. The 4.6-fold elevation in incidence of Mer- status in brain tumor patients is highly significant (chi2 = 24; p < or = 0.001). MGMT activity was independent of age in the lymphocytes of brain tumor patients and was present in lymphocytes from six of nine tumor patients whose normal brain specimen was Mer-. DNA polymerase beta, apurinic/apyrimidinic endonuclease, and lactate dehydrogenase activities were present in all specimens tested, including Mer- specimens from brain tumor patients. Our data are consistent with a model of carcinogenesis in human brain in which epigenetically regulated lack of MGMT is a predisposing factor and alkylation-related mutagenesis is a driving force.
...
PMID:Lack of the DNA repair protein O6-methylguanine-DNA methyltransferase in histologically normal brain adjacent to primary human brain tumors. 869 23

Mouse renal cell tumors (RCT) were induced in male CBA male mice by 5 subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH) per kg body weight once a week. After a lag period of two years the kidneys were removed, and serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: Glycogen content, basophilia, and activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malic enzyme (ME), succinate dehydrogenase (SDH), alkaline phosphatase (ALPase) and glutamyl-transpeptidase (GGT). RCT displayed the same histochemical profile irrespective of their size and growth pattern. In comparison with normal kidney epithelium, the neoplastic cells exhibited elevated activities of enzymes for glycolysis (HK, PK LDH) and the pentose phosphate pathway (G6PDH) while negative G6Pase and low SDH activity were observed in these cells. The majority of RCT showed high PHO activity and weak staining for SYN. Activities of ALPase and GGT were negative in most of the RCT. Giant cells were detected in some large RCT. Higher activities of glycolytic and mitochondrial enzymes and G6PDH were found in giant cells compared with other tumor cells. Tubular preneoplastic lesions were similar to neoplastic lesions in morphological and histochemical characteristics. The present study revealed that a markedly elevated capacity for glycolysis and the pentose phosphate pathway occurred in renal cell tumors in mice. A similar histochemical pattern in the few preneoplastic tubular lesions observed suggests that these metabolic aberrations emerge early in carcinogenesis, but studies on earlier stages of renal carcinogenesis are needed to substantiate this assumption.
...
PMID:[Enzymic spectrum of preneoplastic and neoplastic changes induced by 1,2-dimethylhydrazine in mouse kidneys]. 874 89

Diallyl sulfide (DAS), a major flavour component of garlic, is known to modulate drug metabolism and may protect animals from chemically induced toxicity and carcinogenesis. In this study the effects of DAS on the oxidative metabolism and hepatotoxicity induced by acetaminophen (APAP) in rats were investigated. In the hepatotoxicity evaluation of Fischer 344 rats there was a dose-dependent increase in the odds of mortality rate by APAP (P = 0.009); DAS treatment significantly protected rats from APAP-related mortality (P = 0.026). Liver toxicity determined by lactate dehydrogenase activity was significantly increased by APAP treatment (0.75 g/kg). Pretreatment with DAS protected animals from APAP-induced liver toxicity in a time- and dose-dependent fashion. Treatment of DAS (50 mg/kg) 3 hr after APAP dosing significantly (P < 0.05) protected rats from APAP-induced liver toxicity. The metabolism of APAP (50 microM) in vitro was significantly inhibited by DAS (0.3-1 mM) in liver microsomes isolated from F344 rats. As the effect of DAS on APAP-induced hepatotoxicity in vivo was observed only when DAS was administered before or shortly after (< 3 hr) APAP dosing, data suggested that the protective effect of DAS is mainly at the metabolic activation step of APAP. However, the possibility that DAS may also have effects on other drug metabolism systems, such as glutathione (GSH) and glutathione S-transferases, cannot be ruled out.
...
PMID:Protective effects of diallyl sulfide on acetaminophen-induced toxicities. 901 71

Urinary enzyme levels were investigated in rats administered different promoters in their diet for 32 weeks after being initiated by treatment with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks. All groups were composed of 10 rats each. Group 1: females treated with 3% uracil (100% carcinoma incidence). Group 2: control females kept on basal diet only (0% carcinoma incidence). Group 3: males treated with 5% sodium L-ascorbate (100% carcinoma incidence). Group 4: control males (0% carcinoma incidence). Urine was collected at the end of weeks 12, 24 and 36 and tested for lactate dehydrogenase (LDH), alkaline phosphatase, N-acetyl-beta-D-glucosaminase and aspartate aminotransferase activity. To facilitate comparison, data were related to the corresponding excreted creatinine levels. All measurements were made using a centrifugal automatic analyzer. The urine of rats with cancer lesions (groups 1 and 3) showed significant elevation in all enzyme activities at weeks 24 and/or 36 except for LDH in females (group 1). The M/H ratio of the LDH isozymes was reversed (1.10 +/- 0.10) in the tested rats with carcinomas at week 36. This study thus provides evidence of a correlation between high urinary enzyme levels and cancer development in the rat bladder. Measurement of the tested enzymes might thus provide a method to detect malignant changes in bladder epithelium by direct urine analysis.
Carcinogenesis 1999 Jul
PMID:Elevation of urinary enzyme levels in rat bladder carcinogenesis. 1038 97

The modifying effects of auraptene isolated from the peel of citrus fruit (Citrus natsudaidai Hayata) on macrophage and lymphocyte functions were investigated in mice. Female BALB/c mice were gavaged with auraptene at a dose of 100, 200 or 400 mg/kg once a day for 10 consecutive days. Glucose consumption of peritoneal macrophages was significantly higher than that in the control group (P < 0.05-0.001) in auraptene-treated mice at all doses at 24, 48 and 72 h incubation except for mice given 200 mg/kg auraptene at 24 h incubation. Activity of acid phosphatase in peritoneal macrophages was significantly increased in mice treated with auraptene at a dose level of 100 mg/kg (P < 0.001). Activity of beta-glucuronidase in peritoneal macrophages in the auraptene-treated mice at all doses was significantly higher than that in the control group (P < 0.001), but there was no significant difference in lactate dehydrogenase activity of peritoneal macrophages at any dose. Interleukin (IL)-1beta production of peritoneal macrophages in the auraptene-treated mice at all doses was significantly higher than that in the control group (P < 0.05-0.001). Tumor necrosis factor alpha production of peritoneal macrophages in mice gavaged with auraptene at a dose of 200 mg/kg was significantly higher than that in the control group (P < 0.05). Auraptene did not affect proliferation of spontaneous splenic lymphocytes in mice at any dose. Stimulation indices in mice given auraptene at a dose of 200 mg/kg were significantly higher than that in the control group (P < 0.05). When spleenic lymphocytes were cultured without concanavalin A (Con A), IL-2 and interferon (IFN) gamma productions were not detectable in the supernatant. However, IL-2 and IFN production stimulated by Con A were significantly increased in mice gavaged with auraptene at dose levels of 100 and 200 mg/kg (P 0.05-0.001). Auraptene did not enhance spontaneous IL-4 production by splenocytes. There was no significant difference in IL-4 production of splenic lymphocytes stimulated by Con A in all groups. These findings might suggest that oral administration of citrus auraptene effectively enhanced macrophage and lymphocyte functions in mice.
Carcinogenesis 1999 Aug
PMID:Immunomodulatory action of citrus auraptene on macrophage functions and cytokine production of lymphocytes in female BALB/c mice. 1042 94

There are about 600 million betel quid (BQ) chewers in the world. BQ chewing is associated with increased incidence of oral cancer and submucous fibrosis. In this study, areca nut (AN) extract (200-800 microg/ml) induced the prostaglandin E(2) (PGE(2)) production by 1. 4-3.4-fold and 6-keto-PGF(1 alpha) production by 1.1-1.7-fold of gingival keratinocytes (GK), respectively, following 24 h of exposure. Exposure of GK to AN extract (>400 microg/ml) led to cell retraction and intracellular vacuoles formation. At concentrations of 800 and 1200 microg/ml, AN extract induced cell death at 21-24 and 32-52% as detected by MTT assay and cellular lactate dehydrogenase release, respectively. Interestingly, AN-induced morphological changes of GK are reversible. GK can still proliferate following exposure to AN extract. Cytotoxicity of AN extract cannot be inhibited by indomethacin (1 microM) and aspirin (50 microM), indicating that prostaglandin (PG) production is not the major factor responsible for AN cytotoxicity. PGE(2) exhibited little effect on the growth of GK at concentrations ranging from 100-1000 pg/ml. Stimulating GK production of PGs by AN extract could be due to induction of cyclooxygenase-2 (COX-2) mRNA expression and protein production. These results suggest that AN ingredients are critical in the pathogenesis of oral submucous fibrosis and oral cancer via their stimulatory effects on the PGs, COX-2 production and associated tissue inflammatory responses. AN cytotoxicity to GK is not directly mediated by COX-2 stimulation and PG production.
Carcinogenesis 2000 Jul
PMID:Areca nut extract up-regulates prostaglandin production, cyclooxygenase-2 mRNA and protein expression of human oral keratinocytes. 1087 15

Communication between mitochondria and the nucleus is important for a variety of cellular processes such as carbohydrate and nitrogen metabolism, mating and sporulation, and cell growth and morphogenesis. It has long been known that the functional state of mitochondria can influence nuclear gene expression. For example, in yeast cells lacking the mitochondrial genome, the expression of several nuclear genes, such as CIT2 (citrate synthase), MRP13 (mitochondrial ribosomal protein), and DLD3 (d-lactate dehydrogenase) has been reported to be altered. Here we show by microarray analysis of the genome-wide transcription profile of Saccharomyces cerevisiae that yeast petite mutants lacking mitochondrial DNA induce genes coding for mitochondrial proteins, enzymes of the glycolytic pathway and of the citric acid cycle, cell wall components, membrane transporters, and genes normally induced by nutrient deprivation and a variety of stresses. Consistent with the observed induction of genes related to cell stress and those encoding membrane transporters, yeast petite cells showed increased resistance to severe heat shock and exhibited a pleiotropic drug resistance phenotype. The observed changes in nuclear gene expression in cells lacking mitochondrial DNA may have implications for the role of mitochondria in processes such as carcinogenesis and aging.
...
PMID:Interorganellar communication. Altered nuclear gene expression profiles in a yeast mitochondrial dna mutant. 1105 16

Identification of cytogenetic abnormalities is an important clue for the elucidation of carcinogenesis. However, the cytogenetic and clinical significance of adult T-cell leukemia/lymphoma (ATLL) is still unclear. To address this point, cytogenetic findings in 50 cases of ATLL were correlated with clinical characteristics. Karyotypes showed a high degree of diversity and complexity. Aneuploidy and multiple breaks (at least 6) were observed frequently in acute and lymphoma subtypes of ATLL. Breakpoints tended to cluster at specific chromosomal regions, although characteristic cytogenetic subgroups of abnormalities were not found. Of these, aberrations of chromosomes 1p, 1q, 1q10-21, 10p, 10p13, 12q, 14q, and 14q32 correlated with one or more of the following clinical features: hepatosplenomegaly, elevated lactate dehydrogenase, hypercalcemia, and unusual immunophenotype, all indicators of clinical severity of ATLL. Multiple breaks (at least 6); abnormalities of chromosomes 1p, 1p22, 1q, 1q10-21, 2q, 3q, 3q10-12, 3q21, 14q, 14q32, and 17q; and partial loss of chromosomes 2q, 9p, 14p, 14q, and 17q regions correlated with shorter survival. These cytogenetic findings are relevant in predicting clinical outcome and provide useful information to identify chromosomal regions responsible for leukemogenesis. This study also indicates that one model of an oncogenic mechanism, activation of a proto-oncogene by translocation of a T-cell-receptor gene, may not be applicable to the main pathway of development of ATLL and that a multistep process of leukemogenesis is required for the development of ATLL. (Blood. 2001;97:3612-3620)
...
PMID:Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki. 1136 58

Results from recent intervention trials indicated that supplemental beta-carotene enhances lung cancer incidence and mortality among smokers. It was hypothesized that beta-carotene was exerting its deleterious effects through a prooxidant effect in the smoke-exposed lung. To test this hypothesis we examined the interactions of beta-carotene and cigarette smoke in transformed human bronchial epithelial cells. We studied the effects of beta-carotene supplementation on rates of gas phase smoke-induced lipid peroxidation, membrane damage and depletion of endogenous antioxidants in BEAS-2B cells. Gas phase cigarette smoke caused cellular beta-carotene levels to decrease over time. The oxidation of beta-carotene by smoke generated various oxidation products, including 4-nitro-beta-carotene, beta-apo-carotenals and beta-carotene epoxides. Peroxidation of membrane lipids by gas phase smoke progressed at a slower rate than did oxidation of beta-carotene and incorporation of beta-carotene into the cells did not enhance the overall rate of lipid peroxidation. Additionally, lactate dehydrogenase release during smoke exposure was also unaffected by the presence or absence of beta-carotene in cells. beta-Carotene incorporation in cells was not found to accelerate the rates of alpha-tocopherol and glutathione depletion by cigarette smoke. Our results indicate that beta-carotene is more sensitive than lipids to cigarette smoke oxidation, but that this preferential oxidation of beta-carotene does not lead to a prooxidant effect in human bronchial epithelial cells.
Carcinogenesis 2001 Aug
PMID:Interactions of beta-carotene and cigarette smoke in human bronchial epithelial cells. 1147 Jul 45

Respirable quartz has been classified as a human lung carcinogen (IARC, 1997). However, the mechanisms involved in quartz-induced carcinogenesis remain unclear. The aim of the present study was to investigate acute DNA damage in epithelial lung cells from rats exposed to quartz. Since surface reactivity is considered to play a crucial role in the toxicity of quartz, the effect of surface modifying agents polyvinylpyridine-N-oxide (PVNO) and aluminium lactate (AL) was evaluated. Therefore, rats were instilled with quartz (DQ12, 2 mg/rat) or quartz treated with PVNO or AL. After 3 days animals were killed and brochoalveolar lavage (BAL) was performed to evaluate inflammatory cell influx. BAL-fluid levels of lactate dehydrogenase (LDH), alkaline phosphatase (AP) and total protein were used as lung damage markers. Neutrophil activation was assessed by myeloperoxidase (MPO) measurement, and total antioxidant capacity of the BAL-fluid was determined using the TEAC (trolox equivalent antioxidant capacity) assay. Lung epithelial cells were isolated and DNA strand breakage was determined by single cell gel electrophoresis (comet assay). DNA damage was significantly increased in epithelial cells from rats instilled with DQ12, whereas no enhanced DNA strand breakage was observed when quartz was treated with PVNO or AL. Total protein, LDH and TEAC were increased in rats treated with native quartz, and this was inhibited by both coatings. A significant correlation between neutrophil numbers and MPO levels was observed, indicating neutrophil activation. Inhibition of DNA damage by both coatings was paralleled by a reduction of neutrophil influx as well as MPO activity. In this study we provide evidence that modification of the particle surface prevents DNA strand breakage in epithelial lung cells from quartz-exposed rats. Furthermore, the present data show the feasibility of our in vivo model to evaluate the role of inflammation, antioxidant status, and cytotoxicity in particle-induced DNA damage.
Carcinogenesis 2002 Jul
PMID:DNA damage in lung epithelial cells isolated from rats exposed to quartz: role of surface reactivity and neutrophilic inflammation. 1211 67


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---