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Cancer and Human Liver Catalase* EDWARDE. MASON,TING-FONGCHIN, YAOW. Li, ANDSIDNEYE. ZIFFREN (Department, nf Surgery, Stale University of Iowa, College of Medicine, lou-a City, loica) SUMMARY Data presented in the present paper indicate that human liver catalase depression is related to weight loss. A statistical study was first made to determine the catalase activity in correlation of the iodotitrimetric and spectrophotometric methods for biopsy and autopsy samples from cancer and cancer-free patients. Cancer patients had a 22 per cent lower liver catalase activity than cancer-free patients. A two-by-two factorial analysis of variance comparing presence or absence of cancer and weight loss revealed that weight loss accounted for the catalase depression and that, when correc tion was made for the weight loss effect, no additional cancer effect was seen. Distribu tion of catalase in subcellular fractions was also studied and failed to show any sig nificant cancer effect but did demonstrate the relationship between weight loss and catalase depression in the soluble fraction. No effect of sex was observed, which is con sistent with Adams' observations in laboratory animals that, when the male of a species does not show an increased liver catalase as compared with female, no sig nificant depression of liver catalase is observed (2). Studies of liver catalase depression by cancers of men were pioneered in 1910 by Blumen thai and Brahn (6). They reported that the liver catalase activity was very low in human beings who had died as a result of various forms of cancer. Experi mental work prior to 1941 has been summarized by Greenstein (11) and has amply demonstrated that the peroxide-splitting enzyme, catalase, is con siderably reduced in the liver of some strains of mice and rats bearing tumors. The decrease in liver catalase in susceptible animals is progressive with the growth of the tumor. There have been re ports that in some strains of animals depression of catalase did not occur despite rapid tumor growth to a large size (4). When an effect is observed the tumor must grow rapidly and reach a size equal to 5 per cent of the animal's total body weight before the effect can be detected (10). Recently Nakahara and Fukuoka (15) isolated a heat-stable, protein-like catalase-depressing material from human tumors and demonstrated its effect in mice. Nakagawa (14) has isolated a liver catalase-depressing substance from the urine * This work was supported by the J. B. Phillips Memorial Grant for Cancer Research from the American Cancer Society. Appreciation is expressed to Prof. E. F. Mason for proofreading and checking of statistical calculations. Received for publication May 4, 1960. of a cancer patient and the gastric juice of patients with stomach cancer. A comparison between the liver catalase activity of patients with malignant tumors and patients with gastric or duodenal ulcer was reported in 1958 by Kiyota (13). They found a lower catalase activity in the cancer patients but did not evaluate the possible nonspecific ef fect of poor nutrition. A nutritional effect in liver catalase activity of animals has been reported by Van Pilsum (17) in 1957. The specificity of de pression of liver catalase due to cancer in man is therefore still open to question, since malnutrition alone could cause the mild depression observed. It has also been observed by Adams (1) that only the liver catalase of animals which is increased by testosterone is depressed by cancer. The present work was undertaken in three rather distinct phases. Initially an investigation was made to find out whether there was any differ ence between patients with cancer and patients who were operated upon for noncancerous condi tions. At the same time the methods used were evaluated for reliability. Secondly, another im portant factor was examined, namely, the presence of a greater frequency and per cent of weight loss in cancer patients as compared with noncancer patients. This was an amplification in which a twoby-two factorial analysis was used, and the two 1474 Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1960 American Association for Cancer Research. MASON et al.—Cancer and Human Liver Catatase variables, cancer-no cancer and weight loss-no weight loss, were subjected to an analysis of variance after an accumulation of sufficient replications of appropriately selected patients to provide equal numbers of patients in each of the four groups. Finally, the distribution of human liver catalase in the subcellular fractionations was investigated in relation to the effect of cancer and weight loss. Also, an analysis was made of the relationships between the human liver catalase activity and sex. All these findings are consistent with experimental work in certain strains of animals in which liver catalase is not directly in fluenced by cancer. The analysis of data leading to this conclusion and the interpretation of these findings comprise the following presentation. EXPERIMENTAL AND RESULTS PART A A study of arithmetic means and variations of liver catalase activity in cancer and noncancer patients as compared with the statistical cor relation of two analytical methods Selection of patients and samples.—Liver bi opsies were obtained from patients whose opera tive procedure involved exposure of the upper abdomen. Livers from autopsies were obtained when patients were examined within 6 hours of death. Samples were obtained from patients who did not have primary liver disease and from areas containing no metastatic tumor. The specimens were chilled immediately and taken to the labora tory, where a 5 per cent homogenate was prepared in 0.05 M phosphate buffer at pH 6.8 with a Potter-Elvehjem homogenizer surrounded by crushed ice. Methods used in analysis.— 1. The titrimetric method used for these studies is a modification of the method of Sumner and Dounce (7). A 0.05-ml. aliquot of the 5 per cent homogenate was added to 50 ml. of 0.1 M hydrogen peroxide buffered with a 0.0067 M phosphate buffer at pH 6.8 and in an ice-cooled beaker. Stirring was done with a Teflon-covered magnet in a moving magnetic field. Samples of 5 ml. volume were withdrawn from the reaction chamber at 0, 1,2, and 3 minutes and injected into 5 ml. of 2 N sulfuric acid. To each of the samples 10 ml. of 10 per cent potassium iodide and 1 drop of 1 per cent molybdic acid were added. Exactly 3 minutes after the addition of the iodide, titration was carried out with 0.005 M thiosulfate, with a few drops of starch added toward the end of the titration to improve the end-point. A constant artificial lighting was used, since sunlight was observed to affect the titration. 1475 2. For the spectrophotometric method (5) a Beckman Model DU spectrophotometer was used with 1-cm. light path quartz cuvettes. The rate of disappearance of hydrogen peroxide was measured at 240 imi by change in optical density. As a pre liminary step, two cuvettes were prepared with 3 ml. of an appropriately dilute homogenate in 0.5 M phosphate buffer of pH 6.8. At zero time 1 ml. of a 3.5 X 10~2M solution of hydrogen peroxide in buffer was added to one of the cuvettes and 1 ml. of buffer was added to the other as a blank. Optical density measurements were then taken at 10-second intervals for 4 minutes. The unit of catalase activity used is defined by this equation: TT ¿»3 * Id r /-l-l U is the unit of catalase activity per minute per gram of fresh liver sample. I0 is the initial concentration of the thiosulfate. It is the concentration of the thiosulfate at t minutes. T is reaction time in minutes. C is the concentration of homogenate. From Table 1 the mean catalase activity for the seventeen biopsy samples was found to be 22.5 per cent lower in cancer patients than in the patients having no cancer. The correlation between these two methods in 24 samples (autopsy included) was 0.90. It was 0.79 in the seventeen biopsy samples. This indicates a high degree of correlation between these two methods. Although the correlation is higher when the autopsy data are included, the correlation coefficient of 0.79 was sufficiently high in the biopsy data to warrant use of either method for studies of catalase activity in human liver samples obtained from living patients with and without cancer. Subsequent analyses were there fore carried out with the titrimetric method alone. PART B Comparison of cancer and weight loss as they relate to liver catalase activity with use of a two-by-two factorial analysis In Part A we found that the liver catalase activity was 22.5 per cent lower in the cancer patients than in the patients having no cancer. The question remained as to the cause of this de pression in cancer patients. Body weight loss was often present as an evidence of poor nutrition. To determine the relationship of liver catalase activ ity to body weight loss and to cancer, the patients were divided into four groups. These groups of patients were selected as having: (a) less than 10 per cent body weight loss and no cancer, (b) more Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1960 American Association for Cancer Research. 1476 Cancer Research than 10 per cent body weight loss but without cancer, (c) less than 10 per cent body weight loss with cancer, and (¿)more than 10 per cent body weight loss with cancer. Determination of body weight loss was by the history recorded in the patient's hospital record. This usually consisted of both the "present" and "usual" weight and the absolute weight loss plus the time interval of weight loss. Because of variations in body build, obesity, and duration of weight loss, it was con sidered desirable to simply divide the patients into groups as they fell above or below an arbi trary 10 per cent body weight loss and thus to consider weight loss as a categorical rather than an ordered variable. The procedures for the biopsy collection and homogenate preparation were the same as in Part A, but only the iodotitrimetric method was used for determination of catalase activity. Some data from the earlier study were used, as indicated by the identical patients' numbers in the tables. The additional patients Vol. 20, November 1960 were selected preoperatively on the basis of pres ence or absence of cancer or body weight loss, as was required to supply an equal number of reitera tions in the deficient groups for the projected twoby-two factorial analysis. The data used for the analysis of variance are shown in Table 2, and the actual analysis is shown in Table 3. It is assumed that these are random samples from a normal population and that the variance is the same for each portion of this normal population. There are two columns in which cancer and noncancer patients are compared and two rows wherein weight loss and no weight loss are compared. The final analysis culminates in an F value of 4.25 with which these statistics must be compared to determine their significance. F .95 (1,20) = 4.25 (8) indicates that if any of the F ratios are greater than 4.25 they are significant at a confidence level of 95 per cent. It is, there fore, apparent that the two-row means with an F ratio of 10.67 were significantly different, or in TABLE1 DATAFORCOMPARISON OFLIVERCATALASE ACTIVITY IN CANCER ANDCANCER-FREE PATIENTS wtBody Caseno.12345(i789101112131415161718192021222324Age6154466250807768717049687954597378837836812«8282SexMMFMFMFMMFMMFMFMMMFFMMMMPATIENTS'Tumor wt.0.260.530.7500.0000.10¿02050à wt.001.55Ó3163819•j1102231018?tttttDiagnostaPeripheral diseaseGastric vascular ulcerDuodenal ulcerDuodenal ulcerCholecystitisDuodenal ulcerMean noncancerGastric of biopsies, ±44205131145153213162133ins261214170*1 ±37202122192187230194158 carcinomaEsophageal carcinomaEsophageal carcinomaRectal adenocareinomaColonie carcinomaAbdominal carcinomatosisGastric carcinomaPancreatic carcinomaPancreatic carcinomaGastric carcinomaGastric carcinomaMean 302.503.00WENTIFICATIONWt.l«sBody cancerArteriosclerosisAcute of biopsies, tracheobronchitisMultiple abscessesHip diabetesBacterial fracture, endocarditisMean noncancerGastric of autopsies, 4710142*72 + cancerUrinary cancerMean bladder + 37 + 42ACTIVITYSpectro-photometric2282 of autopsies, cancerCATALASETitrimetric221323231280231205*249 * Arithmetic mean of groups ±standard deviation (root mean square deviation), t Autopsy samples. Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1960 American Association for Cancer Research. MASON et al.—Cancer and Human Liver Catalase other words there was a relationship between weight loss and liver catalase activity. The column means representing a comparison between cancer and noncancer were not significantly different. Since only weight loss had an effect, no inter action between weight loss and cancer was to be expected, and none was found. PARTC Subcellular distribution of catalase in patients with the variables cancer-no cancer and and weight loss Although we can be 95 per cent sure that a relationship between weight loss and liver catalase does exist, a statement that cancer does not specifically cause a decrease in liver catalase can not be made with the same degree of confidence. This is inherent in the nature of the statement and in the statistical methods. All one can say is that no relationship could be found. Because it is gen erally believed that toxohormone does depress hu man liver catalase, it seems important to look for such an effect by making use of a more sensitive experimental technic. Since the soluble (nonparticulate, nonsedimentable) catalase is reported to be the only portion of liver cell catalase de pressed early and by the smaller tumor growths in laboratory animals (2, 3, 18), an investigation was made of the activity distribution of catalase in subcellular fractions of human liver, again in cluding patients selected with the variable cancer and weight loss for study. In this experiment a PVP'-sucrose buffer medium (19) (10 per cent polyvinylpyrrolidon and 20 per cent sucrose, at pH 6.8) was used for homogenization, and 0.1 per cent triton-XlOO was added after fractionation to assure dissolution of all the catalase-containing particles. The 5 per cent homogenate was centrifuged at a speed of IS.OOOX? for 30 minutes. The two fractions were then separated, and each was made up to the original volume. The titrimetric method was used for determination of catalase activity in the whole homogenate and in each of the fractions. The data indicating the distribution of human liver catalase activity are shown in the Table 4. Table 4 shows no cancer-specific depression of either the soluble supernatant catalase or the sedimentable particulate catalase. Recovery was only 90.7 per cent in the patients who had both cancer and weight loss. The instability of the enzyme seemed to be slightly greater in the sediment than in the supernatant. An analysis of variance was 1PVP donated by Farbenfabriken Bayer AG, Germany: molecular weight about 70,000. 1477 carried out with the data from column C (Table 4) and again showed a significant (90 per cent confi dence) relationship between weight loss and catalase activity but no evidence of a selective or specific tumor-produced agent which actively de pressed the soluble portion of human liver catalase. The combination of cancer and weight loss was associated with a higher mean soluble catalase level—96—thanwas seen in patients with weight loss and no cancer—-88.These figures are not sig nificantly different and cannot be used to prove that cancer increases liver catalase in patients with weight loss, but they do support the earlier finding that cancer has no significant depressive effect on the catalase of human liver. A Mocancer biopsy A Cancer biopsy O No cancer autopsy •Cancer autopsy 40 80 120 160 200 240 Units by Tilrimetric Method 280 320 CHART1.—Aplot of biopsy and autopsy data for cancer and cancer-free patients with the titrimetric method on the abscissa and the spectrophotometric method on the ordinate. Since the correlation coefficient, r = \/b b', where 6 and 6' are estimates of the regression lines of K on A' and X on Y, these regression lines were drawn with the biopsy data used alone (r = 0.79) and for all the data (r = 0.90). In those strains of laboratory animals which show no depression of liver catalase by cancer there is also no difference in catalase activity be tween the two sexes (2). Cancer-free patients from the present study were, therefore, paired accord ing to weight loss into male and female groups. It was hypothesized that the means of the two populations are equal, and this was tested with the statistic "t" (8) : Zi(male) - X2 (female) + U/AT2) ,-2) -2) = -2.179; = +2.179 Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1960 American Association for Cancer Research. 1478 Cancer Research Since the observed t fell between the limits ex pected when an a of 0.05 was used, there is no reason to doubt that men and women have the same level of liver catalase activity. DISCUSSION The above experimental data suggest that cancer depresses human liver catalase indirectly through the malnutrition produced in the host. That the liver catalase activity in cancer patients is usually lower than in cancer-free patients is con firmed by Part A of the present study, but the cause of the lowering cannot be assigned to a Vol. 20, November 1960 specific effect of cancer. Usually cancer is ac companied by weight loss, as is illustrated in Part B of this study. The patients having more than 10 per cent body weight loss but without cancer showed a significant lowering of liver catalase. By contrast, the patients with cancer but without weight loss showed no significant liver catalase depression. As a result of these analyses which take into consideration the additional variable, weight loss, it is necessary to reject the hypothesis of Blumenthal and Brahn and of Kiyota, neither of whom considered body weight loss. From these results, a new hypothesis is sug- TABLE 2 DATAOFLIVERCATALASE ACTIVITY INPATIENTS CLASSIFIED ACCORDING TOPRESENCE ORABSENCE OFCANCER ANDWEIGHTLoss IDENTIFICATIONCase PATIENTS* lossBody wt.DiagnosisCATALASE no.AgeSexWt. ACTIVITY Group 1—< 10% body weight loss and no cancer 5i1ÃŒ52627505461586649FMMMMM000000060709Group ulcerPeripheral diseaseGastricvascular ulcerDuodenal ulcerPeptic ulcerMeanweight 3822023923116117896*188 + body28293303132485546844949MMFMMF111215162234CholecystitisGastric 2—> 10% cancerGastric loss but without ulcerDuodenal ulcerDuodenal ulcerPyloric obstructionObstructed stomachAbdominal anginaMean231323221237228256*249 + 52 Group 3—< 10% body weight loss with cancer carcinomaColonie 331114343515744954737759MMMMFF(100103050609Group carcinomaPancreatic carcinomaGastric carcinomaColonie carcinomaPancreatic carcinomaMeanbody 10%3616913378487371795968FMMFFM171819223038Gastric 4- > cancerColonie weight loss with carcinomaGastric carcinomaEsophageal carcinomaGastric carcinomaGastric carcinomaEsophageal cancerMean166213183232•220261*213±34166214145133204131»166 + 35 ' See footnote *, Table 1. Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1960 American Association for Cancer Research. MASON*et al.—Cancer and Human Lirer Catatase gested—that cancer has a very mild (if any) specific effect on human liver catalase activity. This does not mean that human cancers do not produce toxohormone, since Nakahara and Fukuoka have iso lated a catalase-depressing material, toxohormone, from human tumors and demonstrated its effect in mice. From Adams' series of papers it appears that in susceptible strains of animals the action of the specific cancer-produced, liver catalase-inhibiting material is to interfere or compete with the testicular and adrenal hormones in their stimulation of increased catalase production. If a strain of animals has the same liver catalase activity regardless of the level of testicular and adrenal hormones, then no cancer catalase-de pressing effect is to be expected. The human sub ject, showing no sexual difference in liver catalase activity, is like those strains of laboratory animals in which liver catalase is not susceptible to de pression by toxohormone. Additional support for this new hypothesis was found in the study of the distribution of human liver catalase in subcellular fractions. Price (16) points out that, if cancer affects liver catalase, the distribution will vary in fractions from cancer as compared with cancer-free animals. He observed that the insoluble fraction was not reduced in the liver of tumor-bearing animals, whereas the catalase of the soluble fraction was reduced to 1479 less than one-third that found in the correspond ing fraction from normal liver. In our experiment, we found no significant effect of cancer on the distribution of human liver catalase. In a later paper Price (9) showed that the ap pearance of activity in the soluble fraction of mice was an artifact, since in the PVP-sucrose medium 80-99 per cent of the activity was in the particulate fraction, depending on the pH of the homogenate. When catalase was obtained directly from the isolated part ¡culatea uniformly high specific activity is found. There is less enzyme in the liver of tumor-bearing animals, but qualitatively it is identical to that found in normal animals. Adams recently has again raised the question of distribu tion of catalase and gives data to indicate that there is a decrease in permeability of the mem brane (3) of catalase-containing particles as a re sult of cancer. It was because of these reports that fractional studies were undertaken and that PVPsucrose medium was used. Since approximately 50 per cent of human liver catalase was found as soluble, nonparticulate catalase, additional com parative studies were carried out in other species with the same homogenate medium and conditions (such as pH, centrifugal force, time and tempera ture for homogenization, etc.) The results were most interesting and will be reported in detail in a separate paper; there was a striking difference in TABLE 3 STATISTICAL ANALYTICAL DATAOFHUMAN LIVERCATALASE ACTIVITY IN TWO-BY-TWO FACTORIAL ANALYSIS: CANCER-NO CANCER ANDBODY WEIGHT Loss-No BODYWEIGHTLoss A: DATA OF TOTAL» cancer1,496 < 10% body loss weight lossNo. > 10% bodyweight 0 1,126.02,622.0Cancer1,276.0 ¿.11904,891.0 994.02,270.0Tot»!2,772.0 B: ANALYSISOF VARIANCE; squares17,670 of How means Column means InteractionSubtotalWithin groups squnre17,670 rati«10.67 5,400 5,400 1 3.27 4301,652K 0.20F 49023,50033 132023Mean ,05056.550D.f.*1 95 il, 20) = 4.35 TotalSum * Degrees of freedom. Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1960 American Association for Cancer Research. 1480 Cancer Research Vol. 20, November 1960 the distribution of catalase in the liver cells of formation, and other substances are probably also different species. In our own laboratory 97 per essential. cent was sedimentable in mice at 18,OOOX<7, In conclusion, human liver catalase did show compared with 50 per cent in man. There was also a demonstrable depression by cancer, but it can be an inactive sedimentable fraction which varied explained on a nonspecific basis. The distribution greatly among species and was released or acti of catalase in human liver was different than in vated by triton-XlOO. toxohormone-responsive animals. There was no The relationship of body weight loss and liver sexual difference in liver catalase activity in man. These latter two findings help to correlate the find catalase depression observed in this study is prob ably due to malnutrition. Nutritional effects have ings in man and those in experimental animals. been documented in the laboratory animal. Iron, Although human liver is relatively insensitive to magnesium, copper (12), isoleucine, tryptophan, toxohormone, this does not invalidate the finding and phenylalanine (17) are all essential to catalase of others that toxohormone is produced by human TABLE 4 SUBCELLULAR DISTRIBUTION' OF LlVER CATALASE IN CANCER-FREE AND CANCER PATIENTS COMPARED WITHBODYWEIGHTLoss IDENTIFICATIONCaseAgeSexWt. PATIENTS' ACTIVITYOrigi nal ment homog18000 XICSTATISTICSDistribution5 —— XIOO 18000X»BSupernatant enate xiooAXIOO A ASedi ARecoveryB+C lo»«Body wt.DiagnosisCATALASE Group 1—<10% body weight loss stoneGall bladder 38394041425835714964FFFMF00099Gall stonesGall stonesPeptic ulcerPyloric obstruction256265248244261115130142138132139131129107114«124 + 134549575150*505449524444*49999910»9594*99 Group 2—>10% body weight less ulcerGall 43444546474857497749MFMMF11U151734Gastric stonesObstructed bladder stomachPseudo tumorSuperior mesentericartery occlusion1992951632148987162761193497121768959»88 ±234358465539*484941474267*4992999397105*97 Group 3—< 10% body weight loss cancerGastric 48495051525874647759MMFFM00355Pulmonary carcinomaPulmonary carcinomaColonie carcinomaColonie carcinoma3751472422032121367314711110021768105105109»121 + 183650615547»505846445153*509496104106101•100 10%Gastric 4—> carcinomaGall 53545556577063794876FMFFM1216161727Group carcinomaPulmonary bladder carcinomaColonie carcinomaGastric carcinomabody loss24718018415726512791055093103728685132»96 weight + 235151523335*444240475550»479391988785»91 * Arithmetic mean of groups + standard deviation. Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1960 American Association for Cancer Research. MASON et al.—Cancer and Human Lirer Caialase 1481 TABLE 5 STATISTICAL ANALYTICAL DATAOF HUMANLIVERCATALASEACTIVITY IN SOLUBLEFRACTION(SUPERNATANT) IN TWO-BY-TWOFACTORIAL ANALYSIS: CANCER-NOCANCERANDBODYWEIGHTLoss-No BODY WEIGHTLoss A. DATA OF TOTALS cancer620 < 10% body weight loss > 10% body weight lossNo. 4411,061Cancer6044781,082Total1,224 9192,143 B. ANALYSISor VARIANCE squares4,651 of Row means Column means InteractionSubtotalWithin square4,651 23 1131619Mean23 1394,81317,75022,563D.f.1 1391,109F groups ratio4.2 0.02 0.10F .90 (1, 16) = 3.07 TotalSum cancers. The mechanism of toxohormone produc tion and action remains a challenge in the human cancer problem. REFERENCES 1. ADAMS,D. H. Mouse Liver Catalase, the Antagonistic Effect of Tumor Tissue upon the Hormonal Control Mechanisms. Brit. J. Cancer, 5:409-16, 1951. 2. . Sex Differences in Tissue Catalase Levels, and Their Relation to the Catalase Depressing Action of Tu mors. Ibid., 10:748-57, 1956. 3. . The Effect of Sarcoma 37 on the Intracellular Dis tribution of Mouse Liver Catalase. Ibid., 13:704-10, 1959. 4. APPLEMAN, D.; SKAVINSKI,E. R.; and STEIN,A. M. Cata lase Studies on Normal and Cancerous Rats. Cancer Re search, 10:498-505, 1950. 5. BEER, R. F., JR., and SIZER,I. W. A Spectrophotometric Method Measuring the Breakdown of Hydrogen Peroxide by Catalase. J. Biol. Chem., 196:133-49, 1952. 6. BLUMENTHAL, F., and BRAUN,B. Die Katalasewirkung in normaler und in carcinomatoser Leber. Ztschr. Krebsforsch., 8:436-40, 1910. 7. COLOWICK,S. P., and KAPLAN,N. O. Methods in Enzymology, 11:775-81, 1955. 8. DIXON,W. J., and MASSET,F. J. Introduction to Statisti cal Analysis, pp. 139-188, 119-124. 2d ed. New York: McGraw-Hill, 1957. 9. GREENFIELD,R. E., and PRICE,V. E. Liver Catalase. J. Bi ol. Chem., 220:607-18, 1956. 10. GREENSTEIN,J. P. 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Essential Amino Acid Deficiency and Enzyme Activity. Arch. Biochem. & Biophys., 68:42-53, 1957. 18. VON EULER, H., and HELLER, L. Katalaseaktivität in Leberfraktionen normaler und sarkomtragender Ratten. F. Krebsforsch., 66:393-406, 1949. 19. WOODS,M. W. Polyvinylpyrrolidone as Adjunct in Centrif ugal Separation and Enzymic Assay of Subcellular Com ponents. Proc. Soc. Exper. Biol. & Med., 87:71-73,1954. Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1960 American Association for Cancer Research. Cancer and Human Liver Catalase Edward E. Mason, Ting-fong Chin, Yao W. Li, et al. Cancer Res 1960;20:1474-1481. Updated version E-mail alerts Reprints and Subscriptions Permissions Access the most recent version of this article at: http://cancerres.aacrjournals.org/content/20/10_Part_1/1474 Sign up to receive free email-alerts related to this article or journal. To order reprints of this article or to subscribe to the journal, contact the AACR Publications Department at [email protected]. To request permission to re-use all or part of this article, contact the AACR Publications Department at [email protected]. Downloaded from cancerres.aacrjournals.org on June 15, 2017. © 1960 American Association for Cancer Research.