Protein thiols in normal and neoplastic human uterine cervix

Abstract

Protein-thiol groups that react with dihydroxydinaphthyl disulphide during a 7 h incubation (so-called reactive protein thiols, PSH,) have been quantitatively measured on sections of human uterine cervix by microcytospectrophotometry.Measurements were made on areas (1 pmz) of epithelium and adjoining stroma in samples of normal cervix, and in samples obtained from patients with dysplasia, carcinoma-in-situ and invasive cancer. The ratio of PSH, in epithelium to stroma is substantially reduced in the pathological conditions compared with normal and in apparently normal adjacent areas. Such changes in PSH, are discussed in relation to the redox balance of the tissue, and free radical disturbances previously described.

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

“…Our previous work on protein thiols in CIN and cervix carcinoma (Slater et al, 1985;Nohammer et al, 1989;Benedetto et al, 1990) …”

Oxidative Stress and HPV Carcinogenesis

“…In a fairly large series of cervical histological samples, an increased level of oxidized protein thiol groups was found in cancer specimens compared to normal or dysplastic tissues, as well as compared to non-neoplastic areas surrounding the neoplastic lesion [107], therebysuggesting that highly oxidant conditions were acting on the cancer cells. Indications that HPV tumors experience an increased oxidative environment were then extended and confirmed by studies reporting on: an increased number of DNA adducts in histological samples forming invasive cervical cancers compared with dysplastic or normal tissue [108,109], the increased levels of thioredoxine reductase (TRX) and of apurynic apyrimidinic excision (APE)/Ref-1 in hypoxic micro-regions of cervical carcinomas [110], and by a growing number of reports correlating the activation or the increased expression of many other antioxidant enzymes with the dysplastic/neoplastic phenotype of cell lines or histological lesions [111,112,113].…”

Quantitative cytospectrophotometric studies on protein thiols and reactive protein disulphides in samples of normal human uterine cervix and on samples obtained from patients with dysplasia or carcinoma-in-situ

“…None of the women involved in this study had been taking oral contraceptives for at least 3 months prior to operation. For details of clinical selection of the patients, and of the tissue sampling procedures see Schauenstein et al (1983) and Slater et al (1985).…”

“…Our objective was to evaluate the differences that occur in such pathological conditions compared with normal cervix. The background to this microspectrophotometric approach has been reported previously (Nohammer et al, 1984); a summary of results for reactive protein thiols has also been published (Slater et al, 1985); results for reactive protein thiols and reactive protein disulphides in invasive cancer will be published separately (Benedetto et al, 1986). …”

“…None of the women involved in this study had been taking oral contraceptives for at least 3 months prior to operation. For details of clinical selection of the patients, and of the tissue sampling procedures see Schauenstein et al (1983) and Slater et al (1985).The following areas of the stained sections were measured where appropriate: (i) normal squamous epithelium (NS-Epi) (ii) apparently normal squamous epithelium (ANS-Epi) in the neighbourhood of dysplastic lesions or carcinoma-in-situ; (iii) dysplastic epithelium (DYS-Epi); (iv) carcinomain-situ (CIS); (v) stroma (St) in the immediate vicinity of the areas described in (i) to (iv): the areas of stroma chosen for measurement were free of muscle, blood vessels and glands. For the purposes of this study all cases of dysplasia (from mild to severe) have been grouped together; for an analysis of changes in PSHr with different grades of dysplasia see Bajardi et al (1983a) …”