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PubMed1985

Concentration-dependent inhibition of development of GGT positive foci in rat liver by the environmental contaminant di(2-ethylhexyl) phthalate.

The ability of di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer and environmental contaminant, to suppress development of putative preneoplastic lesions in rat liver was evaluated. gamma-Glutamyl transpeptidase-positive (GGT+) foci were initiated in the livers of Sprague-Dawley male rats with a single dose of diethylnitrosamine (DEN) following partial hepatectomy. Promotion of foci was commenced by feeding a choline-deficient diet (CD). A group of control rats was fed a choline-supplemented diet (CS). The ability of DEHP to suppress the emergence of GGT+ foci was evaluated by feeding additional groups of rats the CD diet containing either 0.1%, 0.5%, 1.0% or 2.0% DEHP. The CD diet promoted the number of GGT+ foci above levels in control livers. Inclusion of the plasticizer to the levels of 0.5%, 1.0% and 2.0% in the CD diet effectively inhibited the appearance of the foci. However, DEHP was unable to inhibit the promoting effect of the CD diet at a concentration of 0.1%. DEHP's ability to block development of GGT+ foci correlated with its ability to increase liver weight and to induce carnitine acetyltransferase (EC 2.3.1.7), a marker of peroxisome proliferation.

Animals↗

PubMed2006

Intermethod calibration of alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) results: application to Fibrotest and Actitest scores.

Two multi-component scores (Fibrotest and Actitest) have been proposed to evaluate liver fibrosis or necro-inflammatory lesions as an alternative to liver biopsy. This approach requires standardization of alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) determinations. For this purpose, ALT and GGT values were assigned to a multi-enzyme material using the appropriate primary reference procedure. This material was used as a common calibrator for sera from 20 patients with viral hepatitis. Measurements were carried out in 11 laboratories, using their own automated routine methods and compared to results obtained using the primary reference procedure. The expression of results in multiples of the upper reference limit worsened the inter-laboratory variation for both enzymes. The multi-enzyme material was commutable for ALT and GGT determination carried out with six analytical systems. Common calibration significantly improved inter-laboratory consistency, which finally reached 1.8% and 3.3% for ALT and GGT, respectively. For each enzyme, it also permitted the retention of a common reference interval for a set of calibrated methods and the improvement of inter-laboratory coherency of Fibrotest and Actitest scores.

Adult↗

PubMed2001

Increased AST and GGT activity as marker of RT-PCR inhibition in RNA extracts from peripheral blood.

The presence of HCV RNA in PMBC, with simultaneous absence of the virus in the plasma (7.8%), suggests that blood is better material for HCV RNA detection than plasma or serum in the diagnostic procedures of patients with chronic hepatitis C as well as in monitoring the antiviral therapy. We studied 111 patients with chronic hepatitis C (anti-HCV+) and elevated level of at least one biochemical marker: AST, ALAT, GGT, AP and bilirubin. Inhibition of amplification was 2% in plasma and 34% in whole blood samples. We applied modification of extraction to reduce the inhibitory effect on PCR, by introducing additional purification of the RNA extract in the Chomczyński method. After our modification of extraction was applied, inhibition was reduced to 1%. In attempt to identify such inhibitory markers that would label the samples, in which additional RNA extract purification should be applied, we analysed the activity of AST and ALAT enzymes, the key markers for parenchymal liver damage; GGT and AP, the markers for cholestatic hepatitis as well as bilirubin. We observed that the increased GGT and AST activities were correlated with the inhibition of RT-PCR. This correlation was statistically significant; for AST (Mann-Whitney test p = 0.09654 and Kolmogorow-Smirnow test p = 0.01543) and for GGT (Mann-Whitney test p = 0.02419 and Kolmogorow-Smirnow test p = 0.01921).

Alanine Transaminase↗

PubMed1992

Co-variation between biological markers and self-reported alcohol consumption. A two-year study of the relationship between changes in consumption and changes in the biological markers gamma-glutamyl transpeptidase (GGT) and average volume per erythrocyte (MCV) among problem drinkers.

Co-variations between self-reported alcohol consumption and the biological markers MCV (average volume per erythrocyte) and GGT (gamma-glutamyl transpeptidase) over a 2-year period were studied in a group of 84 men and 53 women recruited to out-patient treatment by advertisements in the press. Upon admission, the drinking pattern of the participants during the preceding year was registered in detail. The participants were also medically examined, and blood samples taken. All the participants were followed up by new personal interviews, medical examinations and new blood sampling after 3, 9, 25 and 21 months. For the group as a whole, alcohol consumption was significantly lower at the end of the observation period than at admission. GGT was also decreased, but not MCV. Both self-reported consumption and the values for the biological markers showed large inter-individual and intra-individual variations during the observation period. The biological markers seemed to co-vary to a limited degree with changes in reported consumption. Both GGT and MCV seemed to have a low sensitivity but a high specificity to changes in consumption. Both markers also seemed to be somewhat more useful in identifying decreases than increases in consumption. The markers GGT and MCV should be used with caution in connection with therapeutic counselling to individuals.

Adult↗

PubMed1985

An evaluation of gamma-glutamyl transpeptidase (GGT) and p30 determinations for the identification of semen on postcoital vaginal swabs.

The following study entails the investigation of gamma-glutamyl transpeptidase (GGT) and p30 for the identification of seminal stains in sexual assault cases. A commercial kit was used to test for GGT activity, while p30 was demonstrated with a crossed electrophoresis technique. Specificity, sensitivity, and stability of both markers were studied. Postcoital swabs from lab staff were tested for GGT and p30. In addition, 144 postcoital swabs from case material were tested for p30, spermatozoa, and acid phosphatase. Results show p30 to be a useful semen marker particularly in cases of azoospermia. However, GGT was found to be unsuitable for forensic science casework.

Acid Phosphatase↗

PubMed1994

[Evaluation of an increased blood level of GGT, CDT, methanol, acetone and isopropanol in alcohol intoxicated automobile drivers. Alcoholism indicators instead of medical-psychological examination].

Several thousand blood samples were taken from alcoholized drivers at the Blood Alcohol Examination Centre of the Institute of legal Medicine at Cologne University. These samples showed blood alcohol contents (BAC) as well as GGT, CDT, methanol, acetone and isopropanol levels which indicated alcohol addiction. The blood samples were selected by the drivers' ages and their BAC, but in some cases the GGT also played a role. In the majority of cases 1 or 2 parameters were measured. In 200 cases all four indicators were determined. The four parameters characterize a different problematic drinking behaviour. GGT characterizes chronic, long-term misuse, CDT characterizes occasional misuse, methanol characterizes current addicted drinking and acetone and isopropanol characterize metabolic disorders caused by alcohol. The importance of parameters is thoroughly discussed, also in relation to incorrectly measured positive values and the relation between alcohol consumption and -problems. Methanol values above 10 mg/kg, GGT activities above 100 U/l and CDT levels above 60 U/l provide sufficient proof of there being an alcohol problem which requires treatment. The levels of other indicators need not be above normal to determine this. The proportion of drivers under the influence of alcohol with problematic alcohol levels increases significantly when the BAC is above 2.0 per mille. However, there have been drivers with alcohol problems with lower BAC levels. DUI offenders addicted to alcohol are quite frequently over 40 years old. A correlation between the single indicators and the BAC is rarely found. If a correlation is to be found, it would be most likely with drivers whose BAC lies above 2.0 per mille. The mentioned indicators would detect an alcohol problem from the blood sample taken for the blood alcohol test. Alcohol problems may be detected and treated shortly after the DUI offence. This method is comparatively cheaper than medical-psychological-examinations as well as being based on objective and verifiable parameters.

1-Propanol↗

PubMed1987

Studies on gamma-glutamyl transpeptidase (GGT) after di(2-ethylhexyl) phthalate (DEHP) exposure.

Administration of Di(2-ethylhexyl)phthalate (DEHP) at doses of 250, 500, 1000 and 2000 mg/kg to adult rats was found to significantly increase the activity of gamma-glutamyl transpeptidase (GGT) in liver and serum in a dose-dependent manner. The data indicate that DEHP can be hepatotoxic since an increase in serum GGT levels are indicative of hepatobiliary dysfunction and liver malignancy. An assay of GGT in serum of the individuals exposed to DEHP could be helpful in early detection of liver disorders due to this widely used plasticizer.

Animals↗

PubMed1988

Molecular cloning of Escherichia coli K-12 ggt and rapid isolation of gamma-glutamyltranspeptidase.

Based on the results of mapping of ggt, eight strains were selected from a gene library of E. coli. One of the strains harboring pLC9-12 was found to show 14 times higher gamma-glutamyltranspeptidase activity per cell than the wild type strain. The ggt was subcloned to the BamHI site of pUC18 and the recombinant plasmid pSH101 was obtained. Ggt- phenotype of gamma-glutamyltranspeptidase-deficient mutants was complemented by pSH101. The specific activity of the enzyme in cells harboring pSH101 was 37-fold higher than that in the wild type cells. gamma-Glutamyltranspeptidase was isolated from the periplasmic fraction of the cells by simple two steps and crystallized.

Cloning, Molecular↗

PubMed1987

GGT reduction in beta carotene-inhibition of hamster buccal pouch carcinogenesis.

Levels of activity for gamma glutamyl transpeptidase (GGT) were studied in hamster buccal pouches developing DMBA-induced epidermoid carcinomas and in pouches in which carcinogenesis was inhibited by topical application of beta carotene. The beta carotene acted to inhibit tumor development when applied topically on days alternate to the application of 0.25% DMBA in heavy mineral oil thrice weekly for 22 weeks. Forty male young adult Syrian hamsters were divided into four equal groups. Group 1 had DMBA applied to left buccal pouches thrice weekly. Group 2 had DMBA applied as in Group 1 but also beta carotene thrice weekly on days alternate to the DMBA application. Group 3 animals were painted with only beta carotene and Group 4 animals were untreated controls. The left buccal pouches were dissected at autopsy and divided in half. One half was fixed in formalin, sectioned in paraffin and stained with hematoxylin-eosin for histologic study. The other half was prepared for the histochemical demonstration of GGT activity using epithelial whole mount preparations. GGT activity was found to be reduced in the left buccal pouches of those animals treated with both beta carotene and DMBA when compared to those animals treated with DMBA alone.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1985

Individual differences in plasma ALT, AST and GGT: contributions of genetic and environmental factors, including alcohol consumption.

The causes of individuality of the plasma enzymes alanine aminotransferase (ALT; EC 2.6.1.2), aspartate aminotransferase (AST; EC 2.6.1.1) and gamma-glutamyl transferase (GGT; EC 2.3.2.2) were investigated in a study of 206 pairs of twins. Between-person variance was greater in men than women, while within-person variation was similar in both sexes. Plasma ALT and AST levels were affected by genetic factors, while GGT was affected by some environmental factor shared by co-twins. In the men, alcohol intake had a significant but small effect on all three enzyme levels, and since alcohol consumption was highly heritable, this appeared as a genetic influence on enzyme activities. The major factors involved in the observed correlations between these enzymes were a non-shared environmental factor other than alcohol affecting ALT, AST and GGT, and a genetic factor affecting only ALT and AST.

Adolescent↗

PubMed1999

Limitations of CDT and GGT in detecting relapses in patients attending an alcohol problems clinic.

Biochemical markers of alcohol consumption are useful for the detection and monitoring of problem drinking. Blood samples from 37 patients attending an alcohol treatment clinic were analysed for GGT and %CDT, and results were compared with self-reported periods of abstinence and alcohol consumption. Poor correlation was obtained between GGT and %CDT, and between these assays and self-reported alcohol use. The apparent sensitivity and specificity of GGT (57%, 63%) and %CDT (43%, 88%), were considerably lower than those reported by other workers.

Alcohol Drinking↗

PubMed1998

Reduced serum levels of ALT and GGT and high carbohydrate intake among workers exposed to toluene below the threshold limit values.

We have found decreased serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) levels in human males exposed to toluene at low levels, suggesting that toluene exposure or related factors in lifestyles were likely to have lowering effects on serum ALT and GGT activities between toluene-exposed and the control subjects. The present study was attempted to investigate whether there is any difference in nutrient intakes between the two groups. Biochemical results were also analysed together with nutrient intakes. In agreement with our previous reports, the present data also provided significant evidence of lowered serum ALT and GGT activities in toluene-exposed males after age matching (p < 0.05). Energy intakes from carbohydrate, fat and protein were 64.6%, 22.5% and 12.9% in the toluene-exposed group and 62.0% (p < 0.05), 24.8% (p < 0.05) and 13.2%, respectively, in the controls. Multiple regression analysis indicated that carbohydrate, protein and energy intakes are significantly associated with toluene exposure. No significant differences in alcohol consumption, tobacco use, work intensities and physical activities were found between the two groups. The present results suggest that the toluene exposure at levels generally considered to be safe, probably have some biological effects on the liver and related organs.

Adult↗

PubMed1991

[GGT activity in the blood serum of newborn foals after the absorption of a non-species specific colostrum preparation].

Eight vital, new-born foals were additionally administered a non-species-specific colostrum-substitute via stomach-tube within the first 18 hours of their life. The substitute had been made of cattle-colostrum. These foals as well as a control-group of eight foals constantly had free access to maternal colostrum. Object of measurement was GGT-activity in the blood-serum. The increase of GGT-activity within the first 24 hours after birth was very low in the control-group (up to 25 U/l), and very high in the tested animals (418 +/- 182 U/l). Obviously there is a direct connection between this rise and the absorption of colostral GGT which, compared to the mare is raised to a higher power in the cow.

Animals↗

PubMed1998

Plasma aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH) and gamma-glutamyl transpeptidase (GGT) activities in water buffaloes with experimental subclinical fasciolosis.

The effect of chronic Fasciola hepatica infection on the activity of plasma aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH) and gamma-glutamyl transpeptidase (GGT) was investigated in water buffaloes dosed daily with 60 F. hepatica metacercariae over 20 days. Experimental fluke infection caused no clinical signs but provoked an increase in plasma level of IgG directed against F. hepatica from 4 weeks after infection. There was a significant increase in plasma AST from 6 weeks post-infection. Maximal values were reached at 14 weeks and remained significantly elevated by 23 weeks. Plasma GLDH was significantly elevated from 6 to 21 weeks post-infection. Significant increases in plasma GGT occurred from 8 to 26 weeks post-infection, reaching maximal values at 15 weeks. This study shows that plasma enzyme activities may be useful in studies of fluke-induced liver damage in water buffaloes.

Animals↗

PubMed1997

A new hepatitis C virus-like flavivirus in patients with cryptogenic liver disease associated with elevated GGT and alkaline phosphatase serum levels.

The intriguing co-infection of two flaviviruses (GBV-A and GBV-B) in tamarins and the recent discovery of another flavivirus (GBV-C/HGV) in humans raises the question of the relations between hepatitis C virus (HCV) and GBV-C/HGV. To address this issue the sera of 285 patients with liver disease (102 patients with cryptogenic and 183 with known forms of chronic liver disease) and 19 patients without liver disease were tested for HGV-RNA. GBV-C/HGV-RNA was detected by RT-PCR using primers encompassing 5'NC and NS5 regions and hybridization with specific biotinilated and radiolabelled probes. GBV-C/HGV RNA was found in 11 of 20 (55%) acute hepatitis C patients, in 13 of 117 (11.1%) patients with chronic hepatitis C, in 11 of 27 patients with a liver transplant (40.7%), one of 19 (5.3%) patients with chronic HBV infection, 15 out of 102 (14.7%) patients with cryptogenic liver disease and two out of 19 patients with inflammatory bowel disease. In cryptogenic patients, elevated serum gammaglutamyl transpeptidase (GGT, higher than twice the normal values) and alkaline phosphatase (ALP, above normal values) levels were significantly associated with GBV-C/HGV-RNA infection (P < 0.001). In conclusion GBV-C/HGV appears to be transmitted in humans by blood exposure and to be associated with liver disease in HCV co-infected patients and in a minority of patients with cryptogenic disease. The virus is only occasionally pathogenic for the liver and when liver damage is present; the association with the combined elevation of GGT and APH serum levels might represent a specific feature of the liver tropism of the agent.

Adolescent↗

PubMedDate not supplied

Significance of gamma-glutamyl transferase (GGT) activity measurements in alcohol-induced hepatic injury.

Experimental evidence is presented that the determination of gamma-glutamyl transferase (GGT) activity in serum is useful in the assessment of alcohol-induced liver disease and for demonstrating to patients the toxic effects of their drinking habits on the liver. Serial measurements of GGT activity in serum have also proved valuable in monitoring the progress of therapy as well as alleged abstention from alcohol in the known alcoholic.

Adult↗

PubMed2003

Unique GGT --> GTT mutation at K-ras codon 12 in six human pancreatic cancer cell lines from Chinese patients.

OBJECTIVE: To investigate the K-ras mutation pattern in six pancreatic cancer cell lines from Chinese patients. METHODS: All six cell lines were analyzed for mutation in exon 1 of the K-ras gene by polymerase chain reaction (PCR) and direct sequencing. RESULTS: All 6 pancreatic cancer cell lines had GGT --> GTT mutation at K-ras codon 12 but no mutations at codon 13. CONCLUSION: The unique GGT --> GTT mutation at codon 12 plays a potential role in the carcinogenesis of pancreatic cancers in Chinese.

Adenocarcinoma↗

PubMed1992

GGT to GTT transversions in codon 12 of the K-ras oncogene in rat renal sarcomas induced with nickel subsulfide or nickel subsulfide/iron are consistent with oxidative damage to DNA.

Nickel is a toxic, mutagenic, and carcinogenic metal of significant occupational and environmental concern. Although several cellular targets of nickel have been identified, considerable evidence suggests that it can act indirectly upon DNA by inducing the formation of oxidized purines or pyrimidines that constitute promutagenic lesions. In this study, we examined nickel subsulfide (Ni3S2)- or Ni3S2/iron-induced renal sarcomas in F344 rats for the presence of transforming mutations in the K-ras oncogene. Selective oligonucleotide hybridization analysis of K-ras gene sequences amplified by polymerase chain reaction revealed that 1 of 12 primary tumors induced with Ni3S2 and 7 of 9 primary tumors induced with Ni3S2/iron contained exclusively GGT to GTT activating mutations in codon 12. These mutations are consistent with the known ability of nickel, in the presence of an oxidizing agent, to catalyze formation of 8-hydroxydeoxyguanosine, which in turn promotes misincorporation of dATP opposite the oxidized guanine residue. The presence of GGT to GTT transversions was confirmed by direct sequencing of the polymerase chain reaction products. Sequencing also revealed that there were no transforming mutations in codons 13 or 59-61. Additionally, a direct correlation between shortened tumor latency and the presence of activating ras mutations was noted. These results show that, in rat kidney, Ni3S2 can induce transforming mutations that are consistent with the ability of nickel to produce oxidative lesions and that iron, which exacerbates the extent of cellular oxidative damage, can enhance the frequency of these transforming mutations.

Animals↗