UMLS:C0027651 - FACTA Search

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Query: UMLS:C0027651 (tumor)
685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Properties of aryl hydrocarbon hydroxylase in the microsomes were compared between Morris hepatoma 5123D and the host liver from rats bearing this tumor. Requirement of NADPH for the assay of the enzyme activity was observed, compared to that of NADH, and also the additive effect of NADH on the requirement of NADPH was found in the tumor and liver. Curve of pH optimum of the enzyme activity in tumor and liver differed between the rats treated with corn oil and those with 3-methylcholanthrene, indicating a slight shift of the peak value to alkaline pH in the latter. The same values of the apparent Km for NADPH and NADH were shown for the enzyme from the liver and tumor even 24 hr after the treatment with 3-methylcholanthrene, but a difference in the apparent Km for benzo[a]pyrene was demonstrated between the tumor and the host liver, showing 3.6 approximately 6.6 muM in the former and 9.1 approximately 20 muM in the latter. By the addition of 7,8- or 5,6-benzoflavone to the assay medium for the tumor, the induced enzyme was inhibited noncompetitively, and the constitutive enzyme was enhanced, as demonstrated in the host liver. As observed in the induced enzyme in both tissues, cyclohexene oxide and 1,1,1-trichloropropane oxide slightly increased the activity of the constitutive enzyme in the tumor, in contrast to its inhibition in the host liver.
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PMID:Properties of aryl hydrocarbon hydroxylase in microsomes of Morris hepatoma 5123D and the host liver. 0 50

Several anticancer chemicals containing a quinone group were found to stimulate the aerobic oxidation of NADPH by liver microsomes. The enzyme responsible for the above reaction was identified as NADPH-cytochrome c reductase (EC 1.6.2.4), one of the microsomal flavoproteins. The fact that a catalytic amount (20 micronM) of these anticancer chemicals was sufficient to oxidize all the NADPH (100 micronM) indicates that they function as electron carries from the flavoprotein to molecular oxygen. As a corollary, Mitomycin-C and Carbazilquinone stimulated oxygen uptake by Ehrlich ascites tumor cells in the presence of glucose that Daunomycin and Adriamycin failed to do so, although the reason for it remains to be elucidated. Carbazilquinone, in contrast to others, also stimulated the microsomal NADH oxidation.
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PMID:Stimulation of microsomal NADPH oxidation by quinone group-containing anticancer chemicals. 1 20

The mode of generation of free radicals of daunomycin, adriamycin, and carboquone in the NADPH-rat liver microsome system was studied at room temperature by electron spin resonance (ESR) spectroscopy. ESR signals of all these quinoid anticancer chemicals were detected when dissolved oxygen in the reaction mixture was consumed since the radicals are easilyaut oxidizable. All the radicals had an appreciable lifetime under anaerobic conditions. However, there were differences in the mode of their generation between daunomycin and adriamycin, on the one hand, and carboquone, on the other, with respect to the lag time and the effect of the amount of chemicals, pH of the medium, kind of electron donors, NADPH and NADH, and the presence of excess of DNA. Especially, ESR signal reappeared after the first signal had decreased considerably, in the case of daunomycin and adriamycin but not in carboquone. Intact Ehrlich ascites tumor cells also gave rise to an ESR signal of adriamycin and carboquone, but the former signal was prevented from appearing in the presence of glucose.
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PMID:Electron spin resonance study on the mode of generation of free radicals of daunomycin, adriamycin, and carboquone in NAD(P)H-microsome system. 2 73

After incubation of [4-14C]progesterone with cell-free homogenates of 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced mammary tumor of rats, 20 alpha-hydroxy-4-pregnen-3-one, 5 alpha-pregnane-3,20-dione, 20 alpha-hydroxy-5 alpha-pregnan-3-one, 3 alpha-hydroxy-5 alpha-pregnan-20-one, and 5 alpha-pregnane-3 alpha, 20 alpha-diol were identified as the metabolites. In normal mammary tissue, however, 4-pregnene-3 alpha-diol was isolated in addition to 5 alpha-reduced, and 3 alpha- and 20 alpha-hydroxy metabolites. When radioactive testosterone was employed as a substrate, 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 alpha, 17 beta-diol were obtained as the metabolites of the mammary tumor. In the normal mammary gland, only 4-andorstene 3 alpha, 17 beta-diol was formed as its metabolite. Although the enzyme activities relevant to the metabolism varied among the tumor examined, the activity of 20 alpha-hydroxysteroid dehydrogenase in the mammary tumor was significantly lower than that in the normal mammary gland, whereas the activity of 5 alpha-reductase was higher in some of the mammary tumors than in the normal gland. The 5 alpha-reductase activity in the normal mammary gland was mostly localized in the crude microsomal fraction, whereas the same enzyme activity in the tumor was detected in all the organelle fractions. The activities of 20 alpha-hydroxysteroid dehydrogenase and NADPH-linked 3 alpha-hydroxysteroid dehydrogenase were found mainly in the cytosol fractions of the tumor and the normal tissue. The NADH-linked 3 alpha-hydroxysteroid dehydrogenase activity was detected only in the cytosol fraction of the normal mammary gland, but in the tumor studied, the activity of this enzyme was detected in all the subcellular fractions examined.
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PMID:Steroid metabolism in normal mammary gland and in the dimethylbenzanthracene-induced mammary tumor of rats. 3 97

The enzymes involved in conversion of pregnenolone to testosterone in Leydig cell tumors showed a wide distribution among smooth endoplasmic reticulum (SER), rough endoplasmic reticulum (RER), and cytosol, while these enzymatic activities in normal testes were associated primarily with smooth endoplasmic reticulum. Progesterone, used as a substrate in the presence of an NADPH-generating system, was metabolized to androstenedione and finally to testosterone by microsomes from some strains of tumor which did not form testosterone from exogenous labeled androstenedione. Treatment of microsomal membranes from normal testes with 0.1 M Ca++ and Mg++ caused a marked decrease in 17 beta-dehydrogenase activity, measured as conversion of exogenous [3H]androstenedione to [3H]-testosterone, without serious effects on activities of 3 beta-ol-dehydrogenase or 17 alpha-hydroxylase. Studies of initial velocity kinetics showed that treatment with magnesium ion resulted in a marked reduction in affinity of androstenedione for 17 beta-dehydrogenase while the maximum velocity was the same as in untreated microsomes. Also, experiments using [14C]progesterone and [3H]androstenedione simultaneously as substrates demonstrated that treatment with Mg++ ion made it more difficult for exogenous [3H]androstenedione to reach the active site of 17 beta-ol-dehydrogenase than [14C]androstenedione formed in the microsomal membrane from [14C]progesterone. Microsomal proteins were more easily solubilized and 3 beta-ol-dehydrogenase was more severely influenced by Mg++ ion in tumor membranes than in normal microsomes.
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PMID:The possible roles of membrane organization in the activity of androgen biosynthetic enzymes associated with normal or tumorous mouse Leydig cell microsomes. 3 99

Long-chain alcohols are synthesized in the mouse preputial gland tumor (ESR-586) by NADPH:acyl-CoA oxidoreductase. In this study, a series of labeled acids was tested as substrates for the oxidoreductase in a cell-free system from the tumor, and the distribution of label into alcohols, waxes, and other products was determined. The system contained the labeled acid, an acyl-CoA-generating system, an NADPH-generating system, and tumor homogenate. The highest rates of alcohol synthesis were obtained with palmitic (16:0), heptadecanoic (17:0), stearic (18:0), myristic (14:0), elaidic (18:1 trans), and linoleic (18:2) acids, which yielded, respectively, 151, 124, 102, 76, 65, and 35 pmol alcohol/min per mg protein. Decanoic (10:0), lauric (12:0), oleic (18:1 cis), linolenic (18:3), arachidonic (20:4), and behenic (22:0) acids all gave lower activities. Acyl-CoA formation did not appear to be rate limiting with any of the substrates tested except behenic acid. In addition to the fatty alcohol product, a small amount of fatty aldehyde was formed in the system. Incorporation of the labeled fatty acids into wax esters was examined and the distribution of label between the alcohol and acid components of the waxes was determined. Incubation of [1-(14)C]palmitic acid yielded 3.4% free alcohol, 8.3% alcohol esterified in waxes, and 7.7% palmitoyl groups esterified into waxes, whereas, at the other extreme, [1-(14)C]linolenic acid yielded 0.8%, 0.6%, and 38%, respectively, into the homologous components.-Wykle, R. L., B. Malone, and F. Snyder. Acyl-CoA reductase specificity and synthesis of wax esters in mouse preputial gland tumors.
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PMID:Acyl-CoA reductase specificity and synthesis of wax esters in mouse preputial gland tumors. 3 66

This investigation has established the following: 1. Bleomycin, in combination with mitomycin C or other quinone-containing anticancer agents, stimulated the damage to KB cells in culture. 2. In AH66 tumor-bearing rats, the simultaneous treatments of bleomycin plus mitomycin C extend the lifespan. 3. The bleomycin-induced DNA chain breakage was enhanced by the NADPH-dependent microsomal electron transport system. The enhancement was also observed at the level of isolated nuclei and cells. Vitamin K2 and mitomycin C increased breakage at the cellular level by bleomycin and NADPH. 4. Bleomycin-Cu2+ had tendency to increase the lipid peroxidation reaction by the microsomes. However, the reaction was effectively inhibited by antioxidants. 5. Bleomycin induced aldehyde formation from DNA breakage. The formation was effectively inhibited by scavenging reactions with hydralazine hydrochloride or isoniazid. The possibility of suppressing the side effect of bleomycin was discussed in relation to TBA reactive compounds.
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PMID:Experimental results with the combination of bleomycin plus mitomycin C. 8 3

1. Ethanol metabolism in slices or homogenates of transplantable hepatocellular carcinoma HC-252 (HC-252) was 50 to 60% of the rate found in host liver slices or homogenates when they were expressed per gram of tissue wet weight and 70 to 80% of the liver when the rates were expressed per milligram of tissue protein. At 10 mM ethanol, the activities of alcohol dehydrogenase in tumor and liver supernatants were comparable. 2. Tumor microsomes did not oxidize ethanol in the presence of a NADPH-generating system, indicating the absence of the microsomal ethanol-oxidizing system and catalase-mediated peroxidation of ethanol. The HC-252 microsomes were contaminated with catalase, and acetaldehyde production occurred in the presence of a H2O2-generating system (xanthine oxidase). The virtual absence of ethanol oxidation and drug metabolism (aminopyrine demethylase and aniline hydroxylase) in HC-252 microsomes may be due to the low activities of NADPH-cytochrome c reductase, NADPH oxidase, and NADPH-dependent oxygen uptake. 3. Microsomal oxidation of ethanol was present in Morris hepatoma 5123C, a well-differentiated tumor of intermediate growth rate, while activity was negligible in microsomes from Morris hepatoma 7288CTC, a less differentiated tumor. Microsomal NADPH oxidase was present in the well differentiated tumor 5123C but was lacking in the less differentiated tumor 7288CTC. Several microsomal, mitochondrial, and cytosolic properties of HC-252 are similar to those of Morris hepatoma 7288CTC but differ from those of the more differentiated 5123C tumor and normal liver. 4. The content of mitochondrial protein in HC-252 was only 25% that of liver, and oxygen consumption per gram of tumor was only 28% that of the liver. When corrected for the mitochondrial protein content, oxygen uptake in tumor HC-252 and liver homogenates was comparable. Isolated tumor and liver mitochondria displayed comparable State 4 and 3 rates of oxygen consumption with succinate and glutamate as substrates. The activities of the reconstituted malate-aspartate and alpha-glycerophosphate shuttles were only slightly lower in isolated HC-252 mitochondria compared to liver mitochondria, when shuttles were reconstituted with purified enzymes. 5. Antimycin inhibited alcohol metabolism,and pyruvate stimulated alcohol metabolism, much less in tumor slices than in liver slices, suggesting the presence of an augmented mitochondria-independent, cytosolic mechanism for oxidizing reducing equivalents in the tumor. These factors suggest that oxidation of NADH is the limiting factor in ethanol metabolism. Whereas, in the liver mitochondrial reoxidation is predominant, in HC-252, cytosolic reoxidation of NADH also plays a major role.
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PMID:Ethanol metabolism by a transplantable hepatocellular carcinoma. Role of microsomes and mitochondria. 13 37

Previously, we reported that the properties or microsomal 4-methyl sterol demethylase isolated from liver and Morris hepatomas 5123C and 7777 are grossly similar. The individual enzymic steps of this multicomponent system have now been studied, and the rate-determining step has been determined and shown to be identical for liver and these hepatomas. The rates of microsomal oxidative attacks of the 4alpha-methyl, 4alpha-hydroxymethyl, and 4-aldehydic groups are similar for microsomes prepared from rat liver and hepatoma 7777. The rates of mixed-function oxidative attack appear to increase in the order;--CH3 less than --CH2OH less than --CHO. Furthermore, the hepatic and hepatoma NAD-dependent decarboxylase, which catalyzes the reaction following the three oxidative attacks is similar in properties and velocity. The fifth step, an NADPH-dependent reduction of the 3 ketosteroid that is produced by decarboxylation, is also similar. For both tissues, the latter two reactions, under in vitro conditions, proceed at rates that exceed the initial oxidative process. Thus, for elimination of both of the 4-methyl groups of lanosterol, the 10 individual reactions catalyzed in this multicomponent system are identical in liver and hepatoma 7777 microsomes, and the rate-determining stop for both liver and hepatoma is the inital oxidative attack on the 4alpha-methyl group of cholesterol procursors. When the rate-determining reaction of both liver and hepatoma 7777 microsomes is assayed at different temperatures, the same activation energies and the same characteristic breaks in the arrhenius plots are observed. Thus, for both liver and hepatoma, both the nature and the site of rate determination in this multienzymic system must be similar. Since the microsomal enzymes of liver nad hepatoma appear to be catalytically similar and rate determination appears to be similar, too, the characteristic lact of response of tumor microsomes to treatments in vivo that alter host liver microsomal demethylation activity suggests that the insensitivity of these tumors to dietary cholesterol should not be ascribed to alterations in the catalytic proteins. Evidence in this report suggests that the postmicrosomal supernatant fraction of both liver and hepatoma contains a cytosolic protein that may participate in the regulation of the rate-determining attack of 4alpha-methyl sterol substrates. Thus, either qualitative or quantitative differences between the postmicrosomal supernatant fractions obtained from liver and heptomas may account for the observed differences in rates of cholesterol biosynthesis.
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PMID:Investigation of the rate-determining microsomal reaction of cholesterol biosynthesis from lanosterol in Morris hepatomas and liver. 19 49

The mean latent period for skin tumor production by the carcinogen 15, 16-dihydro-11-methylcyclopenta [alpha] phenanthren-17-one (Compound IVb) in the mouse was 30 weeks for a dose of 60 mug/week and about 45 weeks for 60 mug/week, while at 0.6 mug/week, no tumors were observed during 100 weeks. Simultaneous administration of the closely related noncarcinogen (IVa) (54 mug/week) together with the carcinogen at 60 mug/week had no effect on the mean latent period. Simultaneous administration of a threefold quantity of the microsomal enzyme inhibitor 7, 8-benzoflavone (I) with the carcinogen at the highest dose increased the mean latent period to 38 weeks, while at the intermediate dose it completely suppressed tumor formation. Neither ketone IVa nor IVb bound covalently to calf thymus DNA in vitro without prior metabolic activation. After incubation with rat liver microsomes and NADPH in the presence of air, both ketones bound covalently to added DNA in vitro, the noncarcinogen (IVa) about four times more extensively than the carcinogen (IVb), roughly in proportion to the overall extents to which these ketones were metabolized. In contrast, overall metabolism of the carcinogen (IVb) was somewhat increased by the addition of a threefold quantity of the inhibitor (I) to the incubation mixture, but binding to added DNA was almost completely prevented. These results are discussed in connection with the hypothesis that cellular DNA is the target of the carcinogen (IVb) for tumor initiation.
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PMID:The relationship between metabolism, DNA binding, and carcinogenicity of 15,16-dihydro-11-methylcyclopenta(alpha)phenanthren-17-one in the presence of a microsomal enzyme inhibitor. 23 32

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