Elements in autopsy liver tissue samples from Greenlandic inuit and Danes. V. Selenium measured by X-ray fluorescence spectrometry

The content of selenium in normal liver tissue samples from Greenlandic Inuit was measured and the results compared with those obtained in normal liver tissue samples from Danes. Normal liver tissue samples were obtained at autopsy from 50 Greenlandic Inuit (27 men, 23 women) with a median age of 61 years (range 23–83) and from 74 Danes (44 men, 30 women) with a median age of 60 years (range 15–87). Total liver selenium content was measured by X-ray fluorescence spectrometry. The content of selenium (median) was in Inuit 26.6 mol/kg dry liver (5–95 percentile: 15.2–49.4) and in Danes 17.7 mol/kg dry liver (5–95 percentile: < 3.8–36.5) (p < 0.0001). Liver selenium content displayed no significant gender difference, either in Inuit or Danes. In Inuit men, there was a negative correlation between liver selenium content and age (r_s = −0.39, p < 0.05), whereas Danish men displayed a positive correlation between liver selenium content and age (r_s = 0.37, p = 0.02). There was no correlation in Inuit or Danish women. In Inuit, the median hepatic selenium index (liver selenium content divided by age) was 0.48 and in Danes 0.33 (p = 0.001). There was an inverse correlation between hepatic selenium index and age both in Inuit (r_s = −0.77, p < 0.0001) and in Danes (r_s = −0.47, p < 0.0001). In conclusion, Inuit had a higher liver content of selenium and a higher hepatic selenium index compared with Danes. The more favourable selenium status is due to a higher nutritional selenium intake with fish and meat from sea mammals.     

The association between content of the elements S,Cl, K,Fe, Cu,Zn and Br in normal and cirrhotic liver tissue from Danes and Greenlandic Inuit examined by dual hierarchical clustering analysis

ProjectMeta-analysis of previous studies evaluating associations between content of elements sulphur (S), chlorine (Cl), potassium (K), iron (Fe), copper (Cu), zinc (Zn) and bromine (Br) in normal and cirrhotic autopsy liver tissue samples.ProcedureNormal liver samples from 45 Greenlandic Inuit, median age 60 years and from 71 Danes, median age 61 years. Cirrhotic liver samples from 27 Danes, median age 71 years. Element content was measured using X-ray fluorescence spectrometry. Statistics: Dual hierarchical clustering analysis, creating a dual dendrogram, one clustering element contents according to calculated similarities, one clustering elements according to correlation coefficients between the element contents, both using Euclidian distance and Ward Procedure.ResultsOne dendrogram separated subjects in 7 clusters showing no differences in ethnicity, gender or age. The analysis discriminated between elements in normal and cirrhotic livers. The other dendrogram clustered elements in four clusters: sulphur and chlorine; copper and bromine; potassium and zinc; iron. There were significant correlations between the elements in normal liver samples: S was associated with Cl, K, Br and Zn; Cl with S and Br; K with S, Br and Zn; Cu with Br. Zn with S and K. Br with S, Cl, K and Cu. Fe did not show significant associations with any other element.ConclusionsIn contrast to simple statistical methods, which analyses content of elements separately one by one, dual hierarchical clustering analysis incorporates all elements at the same time and can be used to examine the linkage and interplay between multiple elements in tissue samples.     

An evaluation study of trace element content in colorectal liver metastases and surrounding normal livers by X-ray fluorescence

Background Trace elements are involved in many key pathways involving cell cycle control. The levels of trace metals such as iron, copper, and zinc in colorectal liver metastases have not previously been assessed. Methods The trace element content in snap-frozen cancerous liver tissue from patients who underwent liver resection for colorectal liver metastases was compared with the normal surrounding liver (distant from the cancer) using X-ray fluorescence (XRF). Results X-ray fluorescence was performed on a total of 60 samples from 30 patients. Of these 29 matched pairs (of cancer and normal liver distant from cancer from the same patient) were eligible for univariate analysis. Iron (0.00598 vs. 0.02306), copper (0.00541 vs. 0.00786) and zinc (0.01790 vs. 0.04873) were statistically significantly lower in the cancer tissue than the normal liver. Iron, copper, and zinc were lower in the cancer tissue than in the normal liver in 24/29 (82.8%), 23/29 (79.3%), and 28/29 (96.6%) of cases respectively. Multivariate analysis of the 60 samples revealed that zinc was the only trace element decreased in the cancer tissue after adjusting for the other elements. Zinc levels were not affected by any of the histopathological variables. Conclusion Iron, copper, and zinc are lower in colorectal liver metastases than normal liver. An investigation into the pathways underlying these differences may provide a new understanding of cancer development and possible novel therapeutic targets.     

Mouse liver NAD(P)H:quinone acceptor oxidoreductase: protein sequence analysis by tandem mass spectrometry, cDNA cloning, expression in Escherichia coli, and enzyme activity analysis.

The amino acid sequence of mouse liver NAD(P)H:quinone acceptor oxidoreductase (EC 1.6.99.2) has been determined by tandem mass spectrometry and deduced from the nucleotide sequence of the cDNA encoding for the enzyme. The electrospray mass spectral analyses revealed, as previously reported (Prochaska HJ, Talalay P, 1986, J Biol Chem 261:1372-1378), that the 2 forms--the hydrophilic and hydrophobic forms--of the mouse liver quinone reductase have the same molecular weight. No amino acid sequence differences were found by tandem mass spectral analyses of tryptic peptides of the 2 forms. Moreover, the amino-termini of the mouse enzymes are acetylated as determined by tandem mass spectrometry. Further, only 1 cDNA species encoding for the quinone reductase was found. These results suggest that the 2 forms of the mouse quinone reductase have the same primary sequences, and that any difference between the 2 forms may be attributed to a labile posttranslational modification. Analysis of the mouse quinone reductase cDNA revealed that the enzyme is 273 amino acids long and has a sequence homologous to those of rat and human quinone reductases. In this study, the mouse quinone reductase cDNA was also ligated into a prokaryotic expression plasmid pKK233.2, and the constructed plasmid was used to transform Escherichia coli strain JM109. The E. coli-expressed mouse quinone reductase was purified and characterized. Although mouse quinone reductase has an amino acid sequence similar to those of the rat and human enzymes, the mouse enzyme has a higher NAD(P)H-menadione reductase activity and is less sensitive to flavones and dicoumarol, 2 known inhibitors of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)