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. 1992 Jul;66(1):185–191. doi: 10.1038/bjc.1992.240

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.

S K Jonas 1, C Benedetto 1, A Flatman 1, R H Hammond 1, L Micheletti 1, C Riley 1, P A Riley 1, D J Spargo 1, M Zonca 1, T F Slater 1
PMCID: PMC1977904  PMID: 1637668

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].

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson M. C. The pathology of cervical cancer. Clin Obstet Gynaecol. 1985 Mar;12(1):87–119. [PubMed] [Google Scholar]
  2. Bajardi F., Benedetto C., Nöhammer G., Schauenstein E., Slater T. F. Histophotometrical investigations on the content of protein and protein thiols in the epithelium and stroma of the human uterine cervix. II. Intraepithelial neoplasia. Histochemistry. 1983;78(1):95–100. doi: 10.1007/BF00491115. [DOI] [PubMed] [Google Scholar]
  3. Benedetto C., Bajardi F., Ghiringhello B., Marozio L., Nöhammer G., Phitakpraiwan P., Rojanapo W., Schauenstein E., Slater T. F. Quantitative measurements of the changes in protein thiols in cervical intraepithelial neoplasia and in carcinoma of the human uterine cervix provide evidence for the existence of a biochemical field effect. Cancer Res. 1990 Oct 15;50(20):6663–6667. [PubMed] [Google Scholar]
  4. Blonk D. I. Cytochemical examination of lactic dehydrogenase and glucose-6-phosphate dehydrogenase in smears from the uterine cervix. Acta Cytol. 1969 May;13(5):264–269. [PubMed] [Google Scholar]
  5. Board M., Humm S., Newsholme E. A. Maximum activities of key enzymes of glycolysis, glutaminolysis, pentose phosphate pathway and tricarboxylic acid cycle in normal, neoplastic and suppressed cells. Biochem J. 1990 Jan 15;265(2):503–509. doi: 10.1042/bj2650503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CHAYEN J., BITENSKY L., AVES E. K., JONES G. R., SILCOX A. A., CUNNINGHAM G. J. Histochemical demonstration of 6-phosphogluconate dehydrogenase in proliferating and malignant cells. Nature. 1962 Aug 18;195:714–715. doi: 10.1038/195714b0. [DOI] [PubMed] [Google Scholar]
  7. Cohen S., Way S. Histochemical demonstration of pentose shunt activity in smears from the uterine cervix. Br Med J. 1966 Jan 8;1(5479):88–89. doi: 10.1136/bmj.1.5479.88. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coulton L. A. Temporal relationship between glucose 6-phosphate dehydrogenase activity and DNA-synthesis. Histochemistry. 1977 Jan 24;50(3):207–215. doi: 10.1007/BF00491068. [DOI] [PubMed] [Google Scholar]
  9. Elliott P. M., Tattersall M. H., Coppleson M., Russell P., Wong F., Coates A. S., Solomon H. J., Bannatyne P. M., Atkinson K. H., Murray J. C. Changing character of cervical cancer in young women. BMJ. 1989 Feb 4;298(6669):288–290. doi: 10.1136/bmj.298.6669.288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. GLOCK G. E., McLEAN P. Levels of enzymes of the direct oxidative pathway of carbohydrate metabolism in mammalian tissues and tumours. Biochem J. 1954 Jan;56(1):171–175. doi: 10.1042/bj0560171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Heyden G. Histochemical investigation of malignant cells. Histochemistry. 1974 Jun 5;39(4):327–334. doi: 10.1007/BF00495683. [DOI] [PubMed] [Google Scholar]
  12. Ismail S. M., Colclough A. B., Dinnen J. S., Eakins D., Evans D. M., Gradwell E., O'Sullivan J. P., Summerell J. M., Newcombe R. G. Observer variation in histopathological diagnosis and grading of cervical intraepithelial neoplasia. BMJ. 1989 Mar 18;298(6675):707–710. doi: 10.1136/bmj.298.6675.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Johnson D. B., Rowlands C. J. Diagnosis and treatment of cervical intraepithelial neoplasia in general practice. BMJ. 1989 Oct 28;299(6707):1083–1086. doi: 10.1136/bmj.299.6707.1083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lee J. A., Spargo D. J., Riley P. A. Video absorbtiometry in diagnostic cytology: description of a new technique and a preliminary statistical evaluation. J Clin Pathol. 1991 Sep;44(9):749–752. doi: 10.1136/jcp.44.9.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McDermott E. W., Barron E. T., Smyth P. P., O'Higgins N. J. Premorphological metabolic changes in human breast carcinogenesis. Br J Surg. 1990 Oct;77(10):1179–1182. doi: 10.1002/bjs.1800771029. [DOI] [PubMed] [Google Scholar]
  16. McIndoe W. A., McLean M. R., Jones R. W., Mullins P. R. The invasive potential of carcinoma in situ of the cervix. Obstet Gynecol. 1984 Oct;64(4):451–458. [PubMed] [Google Scholar]
  17. Mistry P., Merazga Y., Spargo D. J., Riley P. A., McBrien D. C. The effects of cisplatin on the concentration of protein thiols and glutathione in the rat kidney. Cancer Chemother Pharmacol. 1991;28(4):277–282. doi: 10.1007/BF00685535. [DOI] [PubMed] [Google Scholar]
  18. Mitchell H., Medley G., Giles G. Cervical cancers diagnosed after negative results on cervical cytology: perspective in the 1980s. BMJ. 1990 Jun 23;300(6740):1622–1626. doi: 10.1136/bmj.300.6740.1622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mitchell H., Medley G. Longitudinal study of women with negative cervical smears according to endocervical status. Lancet. 1991 Feb 2;337(8736):265–267. doi: 10.1016/0140-6736(91)90870-u. [DOI] [PubMed] [Google Scholar]
  20. Nilson B., Andersch B., Hansson G., Heyden G. Histochemical investigation of cervical intraepithelial neoplasia. Arch Gynecol. 1987;240(2):75–79. doi: 10.1007/BF02134039. [DOI] [PubMed] [Google Scholar]
  21. Nöhammer G., Bajardi F., Benedetto C., Kresbach H., Rojanapo W., Schauenstein E., Slater T. F. Histophotometric quantification of the field effect and the extended field effect of tumors. Free Radic Res Commun. 1989;7(3-6):129–137. doi: 10.3109/10715768909087934. [DOI] [PubMed] [Google Scholar]
  22. Pinion S. B., Kennedy J. H., Miller R. W., MacLean A. B. Oncogene expression in cervical intraepithelial neoplasia and invasive cancer of cervix. Lancet. 1991 Apr 6;337(8745):819–820. doi: 10.1016/0140-6736(91)92518-7. [DOI] [PubMed] [Google Scholar]
  23. Rees K. R., Slater T. F., Gibbs D. F., Stagg B. H. A modified assay for 6-phosphogluconate dehydrogenase in samples of vaginal fluid from women with and without gynecologic cancer. Am J Obstet Gynecol. 1970 Jul 15;107(6):857–864. doi: 10.1016/s0002-9378(16)34037-6. [DOI] [PubMed] [Google Scholar]
  24. SLATER T. F., SAWYER B. A colorimetric method for estimating the pyridine nucleotide content of small amounts of animal tissue. Nature. 1962 Feb 3;193:454–456. doi: 10.1038/193454a0. [DOI] [PubMed] [Google Scholar]
  25. Schauenstein E., Bajardi F., Benedetto C., Nöhammer G., Slater T. F. Histophotometrical investigations on the contents of protein and protein thiols of the epithelium and stroma of the human cervix. I. Cases with no apparent neoplastic alterations of the epithelium. Histochemistry. 1983;77(4):465–472. doi: 10.1007/BF00495801. [DOI] [PubMed] [Google Scholar]
  26. Shield P. W., Daunter B., Wright R. G. The Pap smear revisited. Aust N Z J Obstet Gynaecol. 1987 Nov;27(4):269–283. doi: 10.1111/j.1479-828x.1987.tb01008.x. [DOI] [PubMed] [Google Scholar]
  27. Slater T. F., Bajardi F., Benedetto C., Bussolati G., Cianfano S., Dianzani M. U., Ghiringhello B., Nöhammer G., Rojanapo W., Schauenstein E. Protein thiols in normal and neoplastic human uterine cervix. FEBS Lett. 1985 Aug 5;187(2):267–271. doi: 10.1016/0014-5793(85)81256-4. [DOI] [PubMed] [Google Scholar]
  28. Slater T. F., Sawyer B., Sträuli U. An assay procedure for nicotinamide-adenine dinucleotides in rat liver and other tissues. Arch Int Physiol Biochim. 1964 Jun;72(3):427–447. doi: 10.3109/13813456409065351. [DOI] [PubMed] [Google Scholar]
  29. Van Noorden C. J., Tas J. Quantitative aspects of the cytochemical demonstration of glucose-6-phosphate dehydrogenase with tetranitro BT studied in a model system of polyacrylamide films. Histochem J. 1980 Nov;12(6):669–685. doi: 10.1007/BF01012022. [DOI] [PubMed] [Google Scholar]
  30. Weber G. Biochemical strategy of cancer cells and the design of chemotherapy: G. H. A. Clowes Memorial Lecture. Cancer Res. 1983 Aug;43(8):3466–3492. [PubMed] [Google Scholar]
  31. Weber G. Enzymology of cancer cells (first of two parts). N Engl J Med. 1977 Mar 3;296(9):486–492. doi: 10.1056/NEJM197703032960905. [DOI] [PubMed] [Google Scholar]
  32. Widy K., Kierski J. Succinic, lactic, and glucose-6-phosphate dehydrogenases in precancerous and cancerous stages in the uterine cervix. Acta Cytol. 1967 May-Jun;11(3):231–235. [PubMed] [Google Scholar]
  33. Winkelstein W., Jr, Selvin S. Cervical cancer in young Americans. Lancet. 1989 Jun 17;1(8651):1385–1385. doi: 10.1016/s0140-6736(89)92825-0. [DOI] [PubMed] [Google Scholar]
  34. Wolfendale M. R., King S., Usherwood M. M. Abnormal cervical smears: are we in for an epidemic? Br Med J (Clin Res Ed) 1983 Aug 20;287(6391):526–528. doi: 10.1136/bmj.287.6391.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wolfendale M. Cervical samplers. BMJ. 1991 Jun 29;302(6792):1554–1555. doi: 10.1136/bmj.302.6792.1554. [DOI] [PMC free article] [PubMed] [Google Scholar]

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