Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alveolar type II cells were isolated from five human lung specimens obtained during resection or lobectomy and enriched to 63-85% purity. Digestion with Sigma protease type XIV followed by centrifugal elutriation and Percoll density gradient centrifugation yielded 1.2 +/- 0.4 X 10(6) cells/g lung in the type II cell fractions. The activities of some enzymes involved in the metabolism of xenobiotics were determined in these freshly isolated type II cells and compared with activities in alveolar macrophages and fractions of unseparated cells from the same tissue samples. Reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity was similar in the three cell fractions from all five patients (18-29 nmol/mg protein/min). An antibody to rabbit reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase inhibited reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reduction as much as 70% in microsomal preparations of the isolated human pulmonary cells, although this same antibody barely reacted with microsomes of the human cells in a Western blot assay. Epoxide hydrolase activity was highest in the alveolar type II cells (1.08 +/- 0.17 nmol/mg protein/min). This activity was 6 times higher than in the alveolar macrophage or unseparated cell fractions. 7-Ethoxycoumarin deethylase activity, a cytochrome P-450-dependent pathway, was low or undetectable in the three cell fractions. Trace amounts of 7-ethoxyresorufin O-deethylase activity (0.5-1.5 pmol/mg protein/min) were detected in microsomes of the isolated human cells, even though a polycyclic hydrocarbon-inducible cytochrome P-450 which metabolizes 7-ethoxyresorufin (form 6 in rabbits) was not detected immunochemically.
Cancer Res 1986 Oct
PMID:Xenobiotic metabolism in human alveolar type II cells isolated by centrifugal elutriation and density gradient centrifugation. 375 92

cis-Diamminedichloroplatinum (CDDP), a widely used cancer chemotherapeutic agent, has been shown to cause dose-dependent acute renal failure (ARF) probably secondary to a direct nephrotoxic effect on proximal tubule cells. The aim of this study was to determine whether administration of ATP-MgCl2 could ameliorate the deleterious effects of CDDP. Isolated rat kidneys were perfused for 2 hr with a 3.5 g % dextran T-110-Krebs HCO3 solution containing 100 micrograms/ml of CDDP. [3H]Inulin was added to measure GFR. Trace amounts of 14C-methylated cytochrome c (cyt) were added to the perfusate to determine the protein reabsorptive capacity (a sensitive indicator of tubular damage) of isolated perfused rat kidneys. Cyt, inulin radioactivity, and [Na+] were measured in the perfusate and urine in control and CDDP-treated kidneys. In additional experiments, ATP-MgCl2 was added simultaneously (0.3 mM) or 1 hr (2 mM) after CDDP treatment. The results indicate that after 2 hr of perfusion, CDDP treatment led to a marked inhibition of protein reabsorption with only a minimal decrease in Na+ and H2O absorption. Furthermore, GFR was not significantly altered despite a marked diuresis. Post-treatment with ATP-MgCl2 led to partial alleviation of the nephrotoxic effect of CDDP after 1 hr of perfusion. ATP-MgCl2 treatment simultaneously with CDDP, however, fully protected the protein reabsorptive capacity of CDDP-treated kidneys. The potential for administering ATP-MgCl2 simultaneously with CDDP suggests a new therapeutic modality in preventing ARF due to CDDP therapy.
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PMID:Reduction of the drug-induced nephrotoxicity by ATP-MgCl2. 1. Effects on the cis-diamminedichloroplatinum-treated isolated perfused kidneys. 387 63

Liver microsomes of the rat contain a group of hydroxylating enzymes which are coupled to a greater or lesser degree to the electron flow system. In our studies, enzymes believed to be directly associated with the electron flow chain of NADPH, ferricyanide reduction, cytochrome c, cytochrome P-450 and substrate hydroxylation have been observed in livers obtained from normal, tumor-bearing and whole body irradiated rats as well as in Morris hepatoma 7777 and dimethyl-amino-biphenyl induced breast tumors.A significant difference appeared to exist in the activity of NADPH oxidase, NADP-ferricyanide reductase and benzopyrene hydroxylase when normal liver was compared with the liver obtained from a breast-tumor-bearing animal. Both cytochrome P-450 and cytochrome b(5) were decreased in the tumor-bearing animal.Tissue distribution of benzopyrene hydroxylase in normal, lactating and tumor-bearing Wistar rats has been studied.With the exception of NADPH oxidase, the activities of NADP-cytochrome c reductase, NADPH-ferricyanide reductase, benzopyrene hydroxylase and P-450 were markedly different in liver from Morris hepatoma 7777-bearing Buffalo rat when this was compared with homologous tissue obtained from normal Buffalo rat.Whole-body irradiated animals showed increased P-450 and NADPH oxidase activity in liver as a function of irradiation and there further appeared to be a correlation with decreased ferricyanide reductase activity.
Br J Cancer 1971 Mar
PMID:Mixed-function oxidation in tumors. 439 26

Human liver microsomal fractions from 27 renal donors (tissue obtained post mortem) and from six cancer patients (tissue obtained during surgery) were used to investigate human hepatic cytochrome P-450 isozyme compositions. In vitro microsomal metabolism of the R and S enantiomers of warfarin to dehydrowarfarin and 4'-, 6-, 7-, 8-, and 10-hydroxywarfarin is catalyzed by cytochrome P-450 isozymes and was used as the basis for evaluating similarities and differences between human cytochrome P-450 isozyme compositions. The mean hepatic cytochrome P-450 concentration from postmortem samples was not significantly different from that of surgical patients (0.51 +/- 0.16 vs. 0.35 +/- 0.14 nmol/mg protein), but the NADPH-cytochrome P-450 reductase activity of the former was significantly higher than that of the latter (141 +/- 56 vs. 29 +/- 6 nmol cytochrome c reduced/min/mg protein). In general, the microsomal preparations were overall stereoselective for R warfarin metabolism. The stereoselectivities for formation of the individual metabolites of the R enantiomer were 6-, 8-, and 10-hydroxywarfarin and the S enantiomer were 4'- and 7-hydroxywarfarin. Of the 33 microsomal preparations, 21 exhibited qualitatively similar warfarin metabolite profiles with 6R- and 7S-hydroxywarfarin having the highest formation rates. Some of the preparations exhibited markedly different metabolite profiles, the most notable having 10R-hydroxywarfarin as the major metabolite. Based on the known warfarin metabolite profiles of five purified cytochrome P-450 isozymes, the isozyme composition of the microsomes can be estimated. The majority of the microsomal preparations apparently had similar isozyme compositions but some preparations were markedly different.
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PMID:Human hepatic cytochrome P-450 composition as probed by in vitro microsomal metabolism of warfarin. 614 15

Protamine sulfate reversibly inhibits serum-induced mitogenic stimulation of several nontransformed and neoplastic cell types in vitro. Fifty percent inhibition was induced by approximately 120-150 micrograms protamine sulfate/ml. Cells were affected directly, and inhibition depended on the duration of cell exposure. Heparin, chondroitin sulfate, heparan sulfate, and dextran sulfate neutralized protamine sulfate effects during the early stages of treatment. Nontransformed cells [bovine aortic endothelial cells, adult human gingival fibroblasts (strains 423 and 1101), fetal rat skin (strain 921-K) and muscle fibroblasts] required longer exposure to induce inhibition than did neoplastic cells [rat 3-methylcholanthrene-induced fibrosarcoma cell lines (MCA-6 and MCA-9), a macrophage-like cell line (NCTC-3749), Walker 256 rat carcinoma cells (ATCC-CCL-38), rat Morris hepatoma cells (ATCC-CCL-144), murine melanoma cells (B16), and rat bladder squamous cell carcinoma cells (804-G)]. Other polycationic compounds, including histone type VIII-S, poly-L-lysine, poly-L-arginine, and protamine (free base), were also effective inhibitors, whereas the basic proteins cytochrome c and lysozyme had no effect. Poly-L-histidine, poly-L-glutamic acid, poly-L-aspartic acid, and dextran blue also had no inhibitory effect.
J Natl Cancer Inst 1984 Dec
PMID:Protamine sulfate inhibition of serum-induced mitogenic responses: differential effects on normal and neoplastic cells. 621 Mar 90

Blood samples from closely monitored patients at the Veterans Administration Hospital in Houston, Texas, were collected, coded, and sent to Microbiological Associates over an 8-month period. Lymphocytes were isolated and cryopreserved at -190 degrees. Lymphocyte samples were simultaneously thawed, phytohemagglutinin activated, and analyzed for benz(a)anthracene-induced aryl hydrocarbon hydroxylase (AHH) levels, [3H]thymidine incorporation, and reduced nicotinamide adenine dinucleotide-dependent cytochrome b5 (cytochrome c) reductase activity. Determinations were made at both 96 and 120 hr in culture, and peak activities were compared among a total of 51 individuals who expressed such lesions as squamous cell carcinomas (22%), adenocarcinomas (14%), oat cell carcinomas (6%), chronic obstructive pulmonary disease (22%), and other nonmalignant diseases. Of the 14 highest AHH/cytochrome c activities observed, all were found in patients with primary lung cancer. Mean AHH/cytochrome c activities were 0.89 for lung cancer patients (a total of 21) and 0.47 for noncancer patients (a total of 30) (p less than 0.001). No relationship was observed between AHH/cytochrome c activity and age of patient, numbers of cigarettes smoked, family history of cancer, location or histological type of tumor, or level of phytohemagglutinin blastogenesis ([3H]thymidine cpm/cytochrome c). Whether the higher AHH levels are the cause or the result of the primary lung cancer remains to be determined.
Cancer Res 1982 Dec
PMID:Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes. 629 46

Methylation of horse heart cytochrome c has been examined in vitro with [methyl-14C]methanesulfonate (MMS) and [1-methyl-14C]-1-nitrosourea (MNU) as alkylating agents. Analysis of protein hydrolyzates by an automatic amino acid analyzer indicates that, at pH 9.0 with MMS, epsilon-N-monomethyl-lysine is found to be the only major methylated basic amino acid. On the other hand, the identity of the predominant basic amino acid residue which is [methyl-14C]-labeled by MNU cannot be determined at present. Peptide mapping of chymotryptic digests of cytochrome c after reaction with MMS reveals a lack of specificity in methylation of a specific lysine residue in this hemoprotein.
Cancer Lett 1984 May
PMID:Alkylation of protein by methyl methanesulfonate and 1-methyl-1-nitrosourea in vitro. 633 36

Mouse peritoneal macrophages (MPM) from C57BL/6J, BALB/c, A strains, and (BALB/ cfemale X C57BL/ 6Jmale )F1 offspring were treated with the oxidative burst (OB)-stimulant 12-O-tetradecanoylphorbol 13-acetate, and their in vitro tumoricidal, tumorostatic , and OB activities were examined. Paraffin oil-elicited, but not thioglycollate (TG)-elicited, MPM exhibited cytotoxicity only toward Yac-1 cells and cytostatic activity toward Yac-1, EL 4, RBL-5, and RLmale 1 lymphoma cells. This activity was in correlation with the reduced capacity of TG-elicited cells to generate OB products. The toxic effect of such activated MPM was partially inhibited by catalase, superoxide dismutase, cytochrome c, and vitamin E (alpha-tocopherol) and was augmented by horseradish peroxidase and the catalase inhibitor aminotriazole (3-amino-1H-1,2,4-triazole), thus indicating the involvement of oxygen-derived toxic reagents, mainly hydrogen peroxide, in the MPM-mediated damage inflicted on the tumor cells. EL 4 cells incubated with nonstimulated MPM exhibited enhanced growth both in vitro and in vivo, whereas OB-stimulated MPM inhibited the growth of such cells in the same experimental systems.
J Natl Cancer Inst 1984 Jun
PMID:Oxidative burst-dependent tumoricidal and tumorostatic activities of paraffin oil-elicited mouse macrophages. 658 55

Seven isozymes of cytochrome P-450 were tested to establish whether they could N-oxidize azoprocarbazine to form the two isomeric azoxy metabolites after optimizing the reconstitution of various purified isozymes with regard to substrate concentration, exogenous lipid, and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c (P-450) reductase concentration. Two isozymes, cytochromes P-450PB-C (an isozyme present in untreated rats or in rats treated with phenobarbital or beta-naphthoflavone) and P-450 beta NF-B (the major beta-naphthoflavone-induced isozyme), had appreciable turnover numbers for the N-oxidation reaction. The product ratio [N-isopropyl-alpha-(methyl-ONN-azoxy)-p-toluamide formation relative to N-isopropyl-alpha-(methyl-NNO-azoxy)-p-toluamide formation] obtained with cytochrome P-450PB-C was nearly identical to those values obtained with liver microsomes from untreated and phenobarbital-treated rats. In addition, cytochrome P-450 beta NF-B and liver microsomes from beta-naphthoflavone-treated rats had nearly identical product ratios. Specific inhibitory antibodies to four purified isozymes were used to titrate the N-oxidase activity of liver microsomes from untreated, phenobarbital-, pregnenolone-16 alpha-carbonitrile-, or beta-naphthoflavone-treated rats. Anti-cytochrome P-450PB-C globulin inhibited more than 70 to 90% of the formation of N-isopropyl-alpha-(methyl-ONN-azoxy)-p-toluamide in microsomes from untreated, phenobarbital-, and pregnenolone-16 alpha-carbonitrile-treated rats, respectively, but only 20 to 50% of N-isopropyl-alpha-(methyl-NNO-azoxy)-p-toluamide formation. A small amount (25 to 30%) of inhibition was observed with anti-cytochrome P-450PB/PCN-E globulin. Anti-cytochrome P-450 beta NF-B globulin inhibited more than 85% of the synthesis of either azoxy isomer catalyzed by liver microsomes from beta-naphthoflavone-treated rats. These results demonstrate that two isozymes are responsible for the oxidative metabolism of azoprocarbazine and can account for the major portion of this N-oxidase activity in liver microsomes from untreated and phenobarbital-, pregnenolone-16 alpha-carbonitrile-, or beta-naphthoflavone-treated rats.
Cancer Res 1984 Feb
PMID:Major isozymes of rat liver microsomal cytochrome P-450 involved in the N-oxidation of N-isopropyl-alpha-(2-methylazo)-p-toluamide, the azo derivative of procarbazine. 669 59

Hepatic hyperplastic nodules induced in mice by long-term griseofulvin administration were examined for selected microsomal activities and responses to enzyme inducers. Despite a decrease in microsomal cytochrome P-450 in hyperplastic nodules, aminopyrine N-demethylase was at control levels. Benzopyrene hydroxylase activity was slightly lower in microsomes derived from hyperplastic nodules than in those of control liver. Reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase was at control level, but reduced nicotinamide adenine dinucleotide- and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductases and the NADPH-ferricyanide reductase were increased. NADPH-supported lipid peroxidation was lower in microsomes from hyperplastic nodules than in those from control liver, whereas microsomal stearoyl coenzyme A desaturase activity was almost doubled in the nodules. NADPH-cytochrome c reductases isolated and semipurified from hyperplastic nodule and from control liver microsomes showed almost identical affinity for NADPH. Microsomal enzymes of hyperplastic nodules responded readily to phenobarbital induction, but sodium dodecyl sulfate-polyacrylamide gel electrophoresis disclosed differences in the polypeptide patterns in the molecular weight range from 47,000 to 54,000 between microsomes derived from hyperplastic nodules and control livers.
Cancer Res 1980 Jul
PMID:Microsomal mixed-function oxidase and activities of some related enzymes in hyperplastic nodules induced by long-term griseofulvin administration in mouse liver. 738 13


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