The association between cancer and the BB isoenzyme of creatine kinase (CK-BB) was investigated, and the possibility of the role of CK-BB as a tumor marker was assessed. With the use of a specific radioimmunoassay, the concentration of CK-BB was measured in 524 sera (obtained from the National Cancer Institute-Mayo Clinic Serum Diagnostic Bank) from patients with a variety of benign and malignant disorders. In 79 of these sera, the results of radioimmunoassay for CK-BB were compared to those of three radioimmunoassays for prostate acid phosphatase. Abnormal CK-BB concentrations occurred in only about 11% of the 366 cancer patients. Some groups of cancer patients had higher rates; e.g., the CK-BB concentration was elevated in 29% of the prostate cancer patients. However, prostate acid phosphatase was abnormal in 65% of the patients with prostate carcinoma--a considerable higher fraction than that found with CK-BB. Findings in patients with benign and malignant gastrointestinal diseases indicate that CK-BB complements carcinoembryonic antigen data and might be useful as part of a tumor marker panel.

We have previously shown that both parathyroid hormone (PTH) and prostaglandin E2 (PGE2) stimulate the activity of creatine kinase BB (CKBB) in rat bone cells in culture. Therefore, morphologically distinct rat osteogenic sarcoma cells in culture were tested for stimulation of CKBB activity by hormones that regulate skeletal tissues. PTH stimulated CKBB in the osteoblast-like clone ROS 17/2; 1 alpha,25(OH)2D3 inhibited this activity while PGE2, CT and 24R,25(OH)2D3 had no significant effect. PGE2 stimulated CKBB activity in the fibroblast-like clone ROS 24/1, which was unresponsive to PTH, CT and Vitamin D metabolites. 24R,25(OH)2D3 as well as PGE2 (but not PTH, CT or 1 alpha 25(OH)2D3) stimulated CKBB in clone ROS 25/1, suggesting that this fibroblast-like clone has some chondroblast-like character. Both PTH and PGE2 stimulated the brain type isoenzyme of CK (CKBB), although the osteogenic sarcoma cell clones contain a significant proportion of the muscle type of CK (CKMM). Thus, increased CKBB activity can serve as an additional characteristic marker for the action of steroid and polypeptide hormones and for prostaglandins.

Aims/background-In humans there are three phosphoglycerate mutase (PGM, EC 5.4.12.1) isoenzymes (MM, MB and BB) which have similar distribution and developmental pathways to creatine kinase (CK, EC 2.7.3.2) isoenzymes. Total serum PGM activity increases in acute myocardial infarction with the same time course as creatine kinase activity. The present study was undertaken to determine changes in the activity of PGM and its isoenzymes after acute myocardial infarction.Methods-PGM activity was measured spectrophotometrically, by coupling the formation of 2-phosphoglycerate from 3-phosphoglycerate with enolase, pyruvate kinase and lactate dehydrogenase catalysed reactions. Inter- and intra-assay reproducibility was assessed. PGM isoenzyme activities were measured using cellulose acetate electrophoresis.Results-Total PGM activity in serum was increased in patients with a confirmed diagnosis of acute myocardial infarction. PGM activity peaked 12 to 24 hours after the onset of symptoms and returned to normal values within 48 hours. Electrophoretic analysis of serum from healthy subjects showed a band corresponding to BB-PGM and two other artefactual bands that did not correspond to adenylate kinase. After myocardial infarction, BB-PGM activity increased and MB-PGM and MM-PGM could be detected. On immunoblot analysis, normal serum contained an inactive form of MM-PGM with a smaller molecular weight than that of PGM tissue isoenzymes.Conclusions-Total serum PGM activity increased in patients with acute myocardial infarction, following the same temporal course as creatine kinase activity. The increase in MM-PGM and MB-PGM activities in these patients was not as high as expected. It is suggested that PGM isoenzymes, after release into the blood, undergo postsynthetic, probably proteolytic, transformation.

OBJECTIVE

Patients with minimal myocardial injuries who present clinically with unstable angina, early stages of myocardial infarction or myocarditis require different therapy strategies to those without. The newer diagnostic assays for detecting myocardial lesions (cardiac Troponin T and cardiac Troponin I [cTnT, cTnI], glycogenphosphorylase - BB [GPBB]) are reported to be more sensitive and specific than common biochemical markers such as CK and myoglobin. Our study tested whether the recently developed four assays cTnT-ELISA (in vitro), cTnT rapid bedside assay, cTnI rapid bedside assay, and GPBB (Immunoenzymetric assay) are effective in detecting minimal myocardial injuries caused by endomyocardial biopsy. We compared them with CK activity (CK-cat), CK-MB activity (CK-MBcat), CK-MB-concentration (CK-MB-mass) and Myoglobin concentration (Myo-conc.).

METHODS

Twenty-four patients [six female, 18 male, age (mean): 47 years (20-65)] underwent diagnostic endomyocardial biopsy. Between four and six biopsies were taken from the mid-right ventricular aspect of the interventricular septum of the heart. Blood was drawn before catheterization (baseline), 10 min after the biopsy, in the next morning, and in the morning of the second day after (days 1 and 2).

CONCLUSIONS

Because of very low CKcat it was not possible to analyse CK-MBcat with reliable precision. The assay for GPBB and cTnI rapid bedside assay did not indicate this minimal myocardial injury. The CK cat, CK-MB mass, and myoglobin assays indicated significant increase at 10 min after biopsy but remained within reference range. cTnT rapid bedside assay indicated this minimal myocardial injury in 50% (P < 0.05). cTnT-ELISA (in vitro) was increased above the reference limit in 54%. This increase was 3. 6-fold the upper reference limit (P < 0.01). In our study, due to superior discriminating power, cTnT-ELISA (in vitro) was the most sensitive assay for minimal myocardial injuries.

Creatine kinase isoenzyme (CK-BB) measured by mass was used to determine its value in the early diagnosis of prostatic cancer. Sera of patients with prostatic carcinoma of various stages (treated and untreated) were compared to normal male sera and sera of patients with benign hyperplasia of the prostate (BPH) with respect to CK-BB. The sera were simultaneously tested for PAP content. The sensitivity of the CK-BB-RIA was 1.63 +/- 0.08 microgram/1 and reproducibility in the higher and lower concentration range 7.6% and 10.5%, respectively. CK-BB alone or in combination with PAP is no marker for early detection of prostatic cancer. In individual cases changes occurred similar to those found with a malignant growth of the prostate.

In order to predict the outcome of patients with acute neurological symptoms at discharge, the concentration of creatine kinase isoenzyme BB (CK-BB) was determined by radioimmunoassay in the cerebrospinal fluid (CSF) of 115 consecutive patients. On admission and over the next 3 days the concentration of CK-BB was significantly increased in patients with brain death and other neurological sequelae compared with those with favourable outcome. There was a variation in time in concentrations of CK-BB between diseases causing neurological sequelae. Thus, cerebrovascular haemorrhages caused highest concentrations on admission, but cerebral ischaemia due to cardiac arrest caused highest concentrations 3 days after admission. On admission the CK-BB measurements were highly specific with high predictive value of positive result when distinguishing patients with brain death and other neurological sequelae from those without complications at discharge. However, when distinguishing patients with brain death from those with other neurological sequelae, the test was most specific and had highest predictive value of a positive result 3 days after admission.

Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and creatine kinase-BB (CK-BB) were estimated in blood serum of 75 patients with primary lung carcinoma and of 20 patients with nonmalignant lung diseases. CEA and NSE were determined by immunoenzymatic method using monoclonal antibodies (Abbott CEA-EIA and Roche NSE-EIA) and CK-BB was assayed using kits supplied by Boehringer-Mannheim (Monotest CK-NAC aktiviert). Enhanced levels of CEA were observed in 64% of patients with lung carcinoma, mainly with adenocarcinoma. Increased activities of NSE and CK-BB were obtained in 47% and 39% of patients, respectively, principally of those with small cell carcinoma. The CEA level was dependent on the stage of advanced NSCLC carcinoma and of NSE and CK-BB on the stage of advanced SCLC carcinoma. The complex analysis of the three markers has given 100% specificity of test.

To determine whether creatine kinase-BB isoenzyme would be useful in detecting central nervous system metastases secondary to breast cancer, we measured the cerebrospinal fluid (CSF) activity of creatine kinase (CK) and its BB isoenzyme (CK-BB) in 65 consecutive patients suspected of having CNS involvement. All patients underwent neurological evaluation, computer tomography (CT) scan and/or radionuclide scintigraphy and lumbar puncture with CSF examination. Thirty patients had CNS metastases, of whom 18 had parenchymal brain metastases (MET). Twelve had leptomeningeal carcinomatosis (MC), of whom four also had parenchymal brain metastases. Thirty-four patients were concluded not to have CNS involvement, whereas one was considered equivocal. CK-BB activity was significantly higher in patients with CNS metastases than in those without (P less than 0.05). This difference was primarily related to the fact that patients with MC had a significantly higher CK-BB activity than patients without CNS metastases or patients with parenchymal brain metastases only (P less than 0.01 and P less than 0.05, respectively). Taking 0.20 U/l as a tentative cut-off value (the upper limit range of patients without CNS metastases being 0.19 U/l), 10 out of 12 patients with MC had activities above this level. The sensitivity and specificity for having MC were 83% and 87%, and the positive and negative predictive values 60% and 96%, respectively. The sensitivity and negative predictive value for having any CNS metastases were 57% and 72%. Specificity and positive predictive value: 100%. The CSF activity of CK-BB appears to be a contribution in the diagnosis of MC secondary to breast cancer and seems superior to protein and LDH.

We assessed the changes in sensitivity and specificity of creatine kinase (CK) isoenzymes at various times after acute myocardial infarction. CK-B was measured by an immunoinhibition technique. CK-MB was measured both by column chromatography on Sephadex DEAE A-50 and by electrophoresis on agarose gel. For CK-B, the sensitivity in detecting infarct varied from 11% in the first 8 h after onset of symptoms to 80% at 32 h after the infarct. Sensitivities for CK-MB by column and by electrophoresis were 25 and 45% for the first 8-h period and 80 and 89% at the 32nd hour, respectively. Comparison of values for CK-B with values for CK-MB by column and by electrophoresis gave correlation coefficients of 0.935 and 0.896, respectively. Patients having macro CK-BB exhibit anomalously high values for CK-B with respect to total CK. Patients having a mild infarct may show no increase in CK-isoenzymes.

Total activities of creatine kinase (EC 2.7.3.2; CK) and lactate dehydrogenase (EC 1.1.1.27; LD) and their isoenzymes were estimated in serum and tissue samples from patients with stomach adenocarcinomas who were to undergo gastric resection. Total CK activity (U/g protein) appeared to be markedly decreased in neoplastic stomach tissue. CK-BB was the predominant isoenzyme in both neoplastic and normal stomach tissues; however, the CK-BB/total CK ratio was increased in adenocarcinoma tissue. Macro CK type 1 was found in two neoplastic tissues and macro CK type 2 in 11. LD4 and LD5 isoenzymes were predominant in gastric tissues, but LD5 and the LD5/LD1 ratio were higher in adenocarcinoma tissue. At 24 h before surgery, CK-BB was demonstrated in sera of all patients and CK-MB in 69%. The CK-BB probably originated from neoplastic stomach tissue, which contains high CK activity, with BB isoenzyme predominating. After gastrectomy, CK and LD isoenzymes in sera were markedly increased by 24 h postsurgery. These alterations were attributed to release from damaged tissue during gastric resection.

Erythrocyte osmotic fragility, serum creatine kinase (CK) and its isoenzymes (CK-MM, CK-MB and CK-BB) were determined in pigs susceptible (SMH) and resistant (RMH) to malignant hyperthermia at three different body weights (Group 1, 10 to 25 kg; Group 2, 26 to 55 kg; Group 3, 56 to 95 kg). The halothane challenge test was used for determining susceptibility to malignant hyperthermia (MH). Significantly (P less than 0.05) greater erythrocyte haemolysis at saline concentrations of 80 to 100 mM NaCl occurred only between SMH and RMH pigs for body weight group 2. The determination of blood enzyme activities revealed also a significant (P less than 0.001) increase for total CK, CK-MM and CK-BB in SMH and RMH pigs of body weight Group 2. Furthermore in SMH pigs, total CK, CK-MM and CK-MB activities were significantly (P less than 0.05) greater in the animals of body weight Group 2. It was concluded that, in SMH pigs, weighing between 26 and 55 kg, there is a relationship between erythrocyte osmotic fragility, plasma CK, CK isoenzyme activities and muscle development.

METHODS

An investigation of creatine kinase (CK)-BB isoenzyme activity in cerebrospinal fluid (CSF) of the rabbits after experimentally induced spinal stenosis.

OBJECTIVE

To create a lumbar spinal stenosis (LSS) model at conus medullaris level without laminectomy in rabbits and to investigate the importance of CK-BB isoenzyme activity in CSF associated with electrophysiologic and histopathologic changes in the spinal cord.

BACKGROUND

LSS is a disorder characterized by leg pain and difficulty of walking. Narrowing of the spinal canal and compression on the spinal cord and nerves are the main features of spinal stenosis.

METHODS

Fifteen male albino rabbits were used in this study. A reproducible, subacute LSS model was created in all rabbits, and CSF CK-BB activity was measured above and below the stenosis level. The electrophysiologic evaluation and the histopathologic examination of the conus medullaris were also performed in each rabbit.

RESULTS

The CK-BB activity was 71.5% in CSF samples that were obtained below the stenosis. The activity was 44.5% in samples obtained above the stenosis and 43.6% in nonstenotic rabbits. In the electrophysiologic studies, the mean amplitudes were decreased and the latency values were lengthened in all ascending and descending nerve potentials at both sides of the stenosis. The number of the neural cells was decreased and imperception of the nucleolus of neural cells and vacuolar degeneration were observed in the histopathologic examination of conus medullaris.

CONCLUSIONS

The activity of CK-BB isoenzyme was increased in CSF of which the circulation was disturbed as a result of neural ischemia, which was accepted in the pathophysiology of LSS.

The effect of iloprost was investigated in an experimental model of cardiac damage in rats after isoprenaline (isoproterenol) treatment. Iloprost was administered by continuous subcutaneous infusion at a dose of 0.44 micrograms/kg body weight (b.w.)/min over a total period of 9 days. On day 8, 5 mg isoprenaline/kg b.w. was applied subcutaneously to induce the cardiac damage. The determinations of creatine kinase (CK, EC 2.7.3.2) and CK isoenzymes, lactate dehydrogenase (LDH, EC 1.1.1.27) and LDH isoenzymes as well as a-hydroxybutyrate dehydrogenase (a-HBDH, no EC) were performed 2, 6 and 24 h after isoprenaline application. Immediately after the last blood sampling, the animals were sacrificed and the hearts were examined histologically. Iloprost-pretreated animals showed a reduction in the rise in heart-specific isoenzymes CK-MB and LDH1-3 in the serum after isoprenaline application. A decrease in isoenzymes CK-BB and LDH4-5 in the serum was also observed in iloprost-pretreated rats. However, no difference could be detected histologically in the extent of myocardial necrosis between animals treated with isoprenaline alone or in combination with iloprost. These results suggest a biochemical cardioprotective effect of iloprost in this rat model after isoprenaline application and the lack of correlation with histological findings is discussed.

The specificity of neuron-specific enolase (NSE) and creatine kinase BB (CK-BB) for small cell lung cancer (SCLC) was determined by biological and immunohistochemical procedures in lung cancer tissues and cultured cell lines. Average values of extractable NSE and CK-BB of SCLC tissues were significantly higher than those of non-SCLC and normal lung tissues. A large amount of NSE and CK-BB was demonstrated in SCLC cell lines. Immunohistochemical examination showed positive staining for NSE and CK-BB in most cases of SCLC and in a few cases of non-SCLC. From these data NSE and CK-BB should be considered to be highly specific for SCLC. In a clinical study serum values exceeding 10 ng/ml for NSE and 1.5 ng/ml for CK-BB were set as positive for the enzymes. Positive rates in SCLC were 71.4% for NSE and 65.3% for CK-BB, which were significantly higher than those in non-SCLC. All positive cases were in an advanced stage. Consecutive daily NSE determinations during induction chemotherapy showed transient elevation immediately after the initiation of drug administration (tumor lysis syndrome), followed by a decline to normal range in responders. This phenomenon seems to indicate tumor sensitivity to cytotoxic drugs. NSE positive non-SCLC was as sensitive to cytotoxic drugs as SCLC. These findings indicate that lung cancer with elevated serum NSE and CK-BB levels at diagnosis should be strongly suspected of being SCLC in the advanced stage.

BACKGROUND

Coronary artery bypass (CABG) surgery is successfully managed with normothermic cardiopulmonary bypass (CPB) using warm blood cardioplegia. The lack of the protective effect of hypothermia, however, might make the central nervous system vulnerable.

METHODS

Thirty-six patients were randomized into normothermic CPB (36-37 degrees C) (NTCPB group, n=18) and hypothermic CPB (28 degrees C) (HTCPB group, n=18) in order to examine whether normothermic or hypothermic CPB induces the release of the intracellular brain enzymes, creatine kinase (CK), its brain-specific isoenzyme (CK-BB), and neuron-specific enolase (NSE) into cerebrospinal fluid (CSF). In addition, clinical neurologic examination and neuropsychologic assessment were done preoperatively, 5 d and 11-23 mo postoperatively.

RESULTS

One patient in each group suffered a stroke after surgery. Two patients in the normothermic group had minor neurologic complications. The cognitive decline after operation was similar in the NTCPB and HTCPB groups. CSF enzymes from normothermic and hypothermic CABG patients without gross neurologic complications were not significantly higher than CSF enzymes from orthopaedic reference patients. CABG patients with neurologic complications had higher enzyme concentrations. Cognitive decline after the operation correlated statistically significantly with CSF enzyme concentrations in the NTCPB group, but not in the HTCPB group.

CONCLUSIONS

CABG operation without major neurologic complication does not induce the release of CK, CK-BB or NSE enzymes into CSF, irrespective of whether the CPB is normothermic or hypothermic.

We studied the effect of prostate resection on serum creatine kinase (EC 2.7.3.2) and lactate dehydrogenase (EC 1.1.1.27) isoenzymes in 22 patients. Two hours after their operations, two-thirds of these patients had increased total creatine kinase activity. The MB isoenzyme was demonstrated in sera of 66% of the patients and the BB isoenzyme in 76%. MB content varied from 1 to 7% of total creatine kinase activity, the average activity being 7.4 +/- 6 (SD) U/L. BB content varied from 1 to 29% of the total creatine kinase activity, the average activity being 8.5 +/- 5.4 U/L. No patients showed evidence of cardiac damage. In contrast to the enzyme changes associated with cardiac injury, MB isoenzyme seen after prostate resection is usually associated with the appearance of BB activity. In addition, the ratio of lactate dehydrogenase isoenzymes 1 and 2 was "inverted" in only five of the 33 patients, and appeared to corrlate with the degree of hemolysis in the postoperative sera. The prostate contains all three creatine kinase isoenzymes, BB predominating.

Determination of the MB isoenzyme of creatine kinase in patients with acute myocardial infarction may be disturbed by the presence of macro creatine kinase. The relative molecular mass of this form of creatine kinase in human serum is at least threefold that of the ordinary enzyme, and it is more thermostable. Here we describe our method for determination of macro creatine kinases and an easy-to-perform test for differentiating two forms of macro creatine kinase, based on their distinct activation energies. The activation energies of serum enzymes are mostly in the range of 40-65 kJ/mol of substrate. Unlike normal cytoplasmatic creatine kinases and IgG-linked CK-BB (macro creatine kinase type 1) a second form of macro creatine kinase (macro creatine kinase type 2) shows activation energies greater than 80 kJ/mol of substrate. The exact composition of macro creatine kinase type 2 is still unknown, but there is good reason to believe that it is of mitochondrial origin.

Creatine kinase (CK) and creatine kinase BB isoenzyme (CK-BB) activities were measured in ventricular CSF obtained by lateral ventricle cannulation in patients suspected of normal pressure hydrocephalus. Lateral ventricle cannulation resulted in highly and variably elevated CK and CK-BB levels. The results emphasise the interference of these CK and CK-BB elevations in studies on the prognostic value of CSF CK and CK-BB levels in head trauma patients with respect to outcome.

We investigated the diagnostic role of creatine kinase isoenzyme BB (CK-BB) in lung cancer. CK-BB was assayed using a radioimmunological system by saturation with Mallinchrodt double antibody 125I labelled (RIA Quant-CPK-BB). Sensitivity was 97% and specificity 90% in 44 cancers (T2-T3), in 36 non-cancers (chronic bronchitis) and in 48 healthy controls. Mean serum CK-BB values for patients with chronic bronchitis (2.64 +/- 1.1 ng/ml) were virtually the same as in normal subjects. Patients with lung cancer had markedly higher serum CK-BB values (9.17 +/- 2.6 ng/ml) than either the control group (healthy subjects) or the chronic bronchitis patients (p less than 0.01). These results lead us to suggest that CK-BB serum determination might prove useful in screening pulmonary disorders. However, further studies are essential to establish: 1) the relationship between serum levels of the isoenzyme and the histology and stage of the neoplastic disease; 2) the relation between CK-BB and the aggressive potential of the neoplastic clone.

Reactivation of serum creatine kinase isoenzyme BB (CK-BB) with 2-mercaptoethanol and EDTA increased the electrophoretic detection rate of CK-BB from 34% to 78% in 58 hospitalized patients with various malignancies. Patients with solid tumors showed the largest and patients with hematologic malignancies the smallest percentage increase in CK-BB after reactivation. For serum from 50 hospitalized patients without cancer, reactivation resulted in detectable CK-BB in two patients; the CK-BB band was never seen in 15 healthy adults. For reasons unknown, five of eight patients with senile dementia of the Alzheimer's type showed CK-BB in serum after reactivation, as did two of five patients suspected of having this disorder. Serum CK-BB may be a useful tumor marker if reactivation with a thiol and EDTA is used immediately after collection.

New 2-site labeled monoclonal antibody techniques were used to measure serially plasma levels of brain-type creatine kinase (CK-BB), heart-type creatine kinase (CK-MB) and muscle-type creatine kinase (CK-MM) during a 20-hour postoperative period in 24 infants after deep hypothermia and total circulatory arrest used in pediatric cardiac surgery. A control group of 7 children undergoing cardiovascular procedures without extracorporeal circulation or circulatory arrest also were studied. There were marked increases in CK-MB and CK-BB levels in the circulatory arrest group but not in the closed group. CK-BB increased from 3.2 +/- 0.5 to 27 +/- 10 ng/ml and CK-MB from 5.9 +/- 2.1 to 137 +/- 12 ng/ml. The CK-MM concentrations increased from 299 +/- 91 and 194 +/- 49 ng/ml to 1,220 +/- 274 and 1,322 +/- 142 ng/ml in the closed and circulatory arrest groups, respectively. Peak levels of CK-MB and CK-BB occurred an average of 133 and 127 minutes, respectively, after reperfusion. The half-time of CK-BB differed significantly from that of CK-MB (149 +/- 15 vs 359 +/- 20 minutes). The arrest time had a more marked effect on CK-BB concentration than on CK-MB and CK-MM concentrations. Arteriointernal jugular venous concentration differences were consistently negative for CK-BB in the circulatory arrest group, but not for CK-MM and CK-MB.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured the MM and BB isoenzymes of serum creatine kinase (CK) by radioimmunoassay in 89 patients with neuromuscular disorders and 44 definite or possible carriers of Duchenne muscular dystrophy (DMD). The CK-MM isoenzyme was closely associated with total CK enzymatic activity. CK-BB was not as closely correlated with total CK but was usually increased in the inflammatory myopathies and DMD and normal in myasthenia gravis, Guillain-Barré syndrome, and amyotrophic lateral sclerosis as well as in neuropathies in which CK is usually normal. In myopathies, CK-BB may be useful for assessing the level of disease activity or the regenerative component. More study is necessary to assess the role of CK-BB in detection of DMD carriers.

Serum creatine kinase BB (CK-BB) determinations were performed daily in 49 newborn infants of less than 34 weeks gestation to evaluate its usefulness in predicting the occurrence of periventricular-intraventricular haemorrhage (PIVH). Using ultrasound PIVH was detected in 20 infants (41%); five grade I, seven grade II, two grade III, six grade IV (grading according to Papile et al.). Infants who developed severe PIVH (grade IV) during the study period had significantly higher serum CK-BB activities immediately after birth when compared with infants who developed less severe haemorrhages (grades I, II and II) or no PIVH. We postulate that these high serum enzyme activities are caused by perinatal brain cell damage which is an important antecedent of severe PIVH. Therefore, serum CK-BB activities at birth can be used as predictor of severe PIVH.

The sequential changes of creatine kinase (CK) isoenzyme activity in serum and hamster buccal pouch tissue (HBPT) of normal, premalignant, and malignant stages during 13 wk of DMBA induced hamster buccal pouch squamous cell carcinogenesis, were studied. We found that the total CK activity in both serum and HBPT of the DMBA painted groups increased during the premalignant period (3-7 wk), with the peak being at 7 wk, while declining in the malignant period (9-13 wk). No significant difference in the serum and HBPT CK-MM, CK-MB and CK-BB activity, in DMBA-induced carcinogenesis, could be established. However, the macro CK type 2 (MCK-2), a cathodically migrating atypical creatine kinase isoenzyme, initially appeared in the sera and tissues of the 3rd wk DMBA-treated group. Its activity gradually increased during the premalignant and malignant stages, paralleling the increasing number of DMBA applications. There was a correlation between the degree of differentiation, and the size and number of the induced tumors with MCK-2. No MCK-2 could be detected in any of the sera or tissues of the control, nor in the 1st wk DMBA-treated group. We propose that MCK-2 is a potential tumor marker in oral malignancy and its presence may provide valuable information for early diagnosis of a possibly premalignant transforming oral lesion.