Search

Extracellular glutathione peroxidase (E-GPx) is a selenium-dependent enzyme that can reduce hydrogen peroxide and phospholipid hydroperoxides. E-GPx is found in plasma and extracellular fluids such as bronchoalveolar lavage fluid. Because lung is one of the tissues that is capable of synthesizing and secreting E-GPx, the effect of exposure to hyperoxia on E-GPx in plasma and lung were studied in an injury model of hyperoxia exposure in adult mice. Exposure to 100% oxygen for 72 h resulted in an increase of 55% in plasma GPx activity and an increase of 50% in the amount of E-GPx protein in the plasma. Exposure to hyperoxia was also associated with an increase in the amount of E-GPx protein in lungs. The 7-fold increase in the amount of E-GPx protein in lungs was not due to plasma contamination of lungs from mice exposed to hyperoxia. E-GPx in the lung is calculated to account for 10% of lung GPx activity in control mice. However, E-GPx is calculated to account for 45% of lung GPx activity in the lungs of mice exposed to hyperoxia for 72 h. Further studies are needed to determine whether the increase in lung E-GPx is due to changes in translation or stability of E-GPx. The role of E-GPx in protecting the lung from oxidative damage warrants further study.

Immunohistochemical analysis of the protein expression c-myc, ets 1, ets 2, TPR-met, c-fos, c-jun, c-ras-pan, p53, yes, src in 79 samples of normal, metaplastic squamous epithelium, intraepithelial and invasive squamous cell carcinoma of uterine cervix was performed using polyclonal rabbit antibodies to the synthetic peptides homologous active areas of corresponding oncoproteins. Higher content of myc, fos, ets2, p53, ras is noted in metaplasia, dysplasia and in tumours as compared to the normal tissues. Protein myc is revealed in the cytoplasm at a grave dysplasia and in the nucleus in the intraepithelial carcinoma: this may serve as a criterion at a differential diagnosis of these conditions. Expression of the oncoproteins fos, ets2, p53, src in the metaplastic squamous cell carcinoma was higher than in the true squamous cell (ectocervical) carcinoma. When compared to the advanced carcinomas, increase of ets2, p53, and at some degree that of myc, the increase is noted in the latter. Invasive carcinoma with a high level of oncoproteins showed a tendency to the synchronization of myc and ras expression. Poor prognosis was associated with a low level (before treatment) of the expression of the majority of the oncoproteins studied.

The tumours studied were as follows: benign carcinoids, well differentiated carcinomas (atypical carcinoids) and poorly differentiated tumours (small-cell carcinoma with neuroendocrine differentiation). Oncoproteins c-myc, c-fos, c-jun, L-myc, c-sis, c-ras, c-src, c-ets-1, c-met were studied immunohistochemically in the material obtained from 25 patients during the operations. A higher expression of c-fos, c-jun, c-ets-1 and c-met is observed at early stages of progression and that of c-myc and L-myc at later stages. Enhancement of c-myc and L-myc expression correlated with the invasiveness and lymphogenic metastasizing. Co-expression and negative correlation between some oncogenes are established. The data obtained may be used for prognosis and therapy.

Enhancer sequences of human papilloma virus (HPV) type 18 were used for screening of HeLa cells cDNA library in lambda gt11 using the protein binding method. Clones with YB I gene homology sequences were isolated. This gene is coding the protein which binds the regulatory region of Y gene of main histocompatibility complex (HLA 11). The YB I transcripts were revealed in all tested samples of cervical carcinomas. To analyze the protein the rabbit antibodies were produced to synthetic peptide, which corresponds to the most hydrophilic region of the protein. This antipeptide serum allowed to identify the nuclear 42K protein in HeLa cells as well as in normal fibroblasts.

Expression of myc, fos, src, ras and sis oncoproteins was studied in biopsy material of tumors, metastases and "normal" surrounding tissues from patients with different histological types of stomach and lung cancer, melanoma and other malignancy using immunoblotting. Besides, the immunohistochemical distribution of these oncoproteins under lung cancer and precancer conditions was analysed. The oncoproteins expression was significantly higher in cancer as compared with precancer and "normal' surrounding tissues. C-myc and c-fos gene products were detected in all the malignant tissues irrespectively to histogenesis of tumors, while the level of c-myc expression was rather high. The high level of c-fos expression was observed in stomach carcinomas and at early stages of lung tumor progression. C-src and c-sis genes expression varied in tumors of different histogenesis. C-src proteins were found in 60% of lung cancer but it was practically absent in stomach carcinomas and in melanomas. C-sis gene product was observed in some melanomas and lung carcinomas. Ras gene can be activated at early stages of tumor progression of stomach carcinomas and lung adenocarcinomas and at later stages of tumor progression in melanomas and small-cell lung carcinomas. Thus, there are some correlations between oncoprotein expression and tumor tissue histogenesis and progression.

Immunoblotting and immunochemistry were used to study the expression of a c-src gene-encoded protein in human lung tumors. The authors were the first to identify this otherwise rarely expressed protooncogene in as many as 60% of lung malignancies of various histogenesis. The expression of c-src protein was increased not only in neuroendocrine tumors (small-cell cancer and atypical carcinoid) but also in non-small-cell tumors such as adenocarcinoma, bronchoalveolar and squamous-cell lung cancer. A weak correlation between protein expression and degree of cell differentiation was established for squamous-cell tumors. The study failed to identify the oncoprotein in the normal tissue and benign lesions. Immunoblotting using Mab 327 monoclonal antibodies and the immunohistochemical method employing TBR polyclonal serum yielded similar data. To summarize, an increased expression of pp60c-src was observed in lung cancer of various histology.

NADPH: adrenodoxin reductase (E.C. 1.18.1.2) and its complex with adrenodoxin catalyze the aerobic oxidation of NADPH by a number of substituted 2-nitrofurans, 5-nitroimidazoles and p-derivatives of nitrobenzene. The nitrocompounds are reduced via an initial single-electron transfer. Under anaerobic conditions nitrofurans are reduced to the corresponding amines. The rate constants of adrenodoxin oxidation by nitrocompounds vary from 4 x 10(5) to 3 x 10(2) M-1 s-1. A linear correlation between the rate constant logarithm and the single-electron reduction potential at pH 7.0 (E7(1)) of nitrocompounds was observed. The relation between the reactivity and the polarographic half-wave potential (E7(1/2)) is distorted. The reactivity of adrenodoxin reductase is two orders of magnitude lower than that of adrenodoxin.