Increased activity of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase in purified cell suspensions and single cells from the uterine cervix in cervical intraepithelial neoplasia

Abstract

The activities of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase have been measured in squamous epithelial cells of the uterine cervix from normal patients and cases of cervical intraepithelial neoplasia (CIN). A biochemical cycling method, which uses only simple equipment and is suited to routine use and to automation, was applied to cells separated by gradient centrifugation. In addition, cells were examined cytochemically, and the intensity of staining in the cytoplasm of single whole cells was measured using computerised microcytospectrophotometry. Twenty per cent of cells in samples from normal patients (n=61) showed staining intensities above an extinction of 0.15 at 540 nm, compared to 71% of cases of CIN 1 (n=14), 91% of cases of CIN 2 (n=11) and 67% of cases of CIN 3 (n=15). The cytochemical data do not allow definitive distinctions to be made between different grades of CIN whereas the biochemical assay applied to cell lysates shows convincing differences between normal samples and cases of CIN. There are no false negatives for CIN 3 (n=14) and CIN 2 (n=10) and 11% false negatives for CIN 1 (n=9) and 14% of false positives for normal cases (n=21). The results of this preliminary study with reference to automation are discussed [corrected]. Images Figure 1

The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate

“…Thus an efficient PPP is vital for cell progression in rapidly dividing cells [74]. This observation is supported by several reports showing that proliferation in nontransformed tissues [75] as well as in tumor tissues [76] is accompanied by higher G6PD activity. In contrast to nontransformed cells, which produce most ribose 5-phosphate for nucleotide biosynthesis through the oxidative branch of the PPP, in tumor cells the nonoxidative branch has been suggested as an important source for ribose 5-phosphate synthesis as well [36,77,78].…”

The pentose phosphate pathway and cancer

“…Relatively high levels of this enzyme are present in many normal metabolizing tissues, including the liver, adipose, and mammary and adrenal glands 11–14 . Tumor cells also express relatively high levels of this enzyme 15 . In terms of activity regulation, the NADP + /NADPH ratio is one of the main modulators of this enzyme.…”

Nanomaterial-Based Electrochemical and Colorimetric Sensors for On-Site Detection of Small-Molecule Targets

“…79 The conversion of NADH in hyperplasia cancer cells was higher compared to the normal cells. 79 To stimulate the biosynthesis of dopamine and tyrosine hydroxylase by NADH makes it an effective supplement in the treatment of parkinson's disease. 80 An example of another neurodegenerative disorder is Friedreich's ataxia (FRDA) 185 .…”

“…80 Conversion of NADH is also elevated in hyperplasic cancer cells compared to normal cells. 79 In total, this biomolecule is known to participate in more than 300 enzymatic oxidation/reduction reactions in vivo. [71][72][73] Accordingly, tools for sensitive measurement of NADH levels could prove very useful in a variety of diagnostic and prognostic contexts.…”

“…[74][75][76][77] Fluctuations in NADH levels in cells and tissues can correspond with intracellular redox status, 78 apoptosis, 78 neurodegenerative diseases, 73,75,76 and mitochondrial anomalies associated with cancer. 79 Nicotinamide adenine dinucleotide (reduced) also stimulates biosynthesis of dopamine and tyrosine hydroxylase, making it an effective candidate in the treatment of Parkinson's syndrome. 80 Conversion of NADH is also elevated in hyperplasic cancer cells compared to normal cells.…”