Affiliation:
1. Department of Pharmacology, School of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5
Abstract
Glutathione content and the activity of glutathione reductase were examined in ventral prostate and chemically induced 11095 squamous-cell prostatic carcinoma in rats, Castration produced a significant reduction in the levels of reduced (GSH) and oxidized (GSSG) glutathione and glutathione reductase activity in the prostate. Replacement of testosterone (50 mg/kg) daily for 7 days to castrated animals elevated the reduced glutathione level and the activity of glutathione reductase almost to normal limits, Squamous-cell carcinoma was implanted in castrated and intact animals, Tumor growth in normal rats produced a decrease of almost 30% in the weight of the ventral prostate at 21 days post-implantation, although the glutathione levels remained unaffected. Much greater activity of glutathione reductase was detected in the tumor in comparison to the values noted for the normal tissue, The tumor also showed significantly higher values for the GSH/GSSG ratio, No apparent difference could be found in the rate of the growth of tumors whether implanted in normal or castrated animals, The levels of reduced and oxidized glutathione and glutathione reductase activity also seemed identical in tumors obtained from both groups of animals, Administration of testosterone (50 mg/kg) or β-estradiol (2 mg/kg) daily for 11 days to tumor-bearing castrated animals did not alter the levels of glutathione and glutathione reductase activity. A significantly higher level of blood reduced glutathione was found in tumor-bearing rats in comparison to that seen for the normal subjects.
Our results demonstrate that androgen depletion and replacement therapy influence the metabolism of glutathione in rat ventral prostate. Squamous-cell carcinoma of the prostate appears to differ from the normal tissue with respect to the observed androgen effects, There is dissimilarity in the metabolism of glutathione in the two tissues since greater activity of glutathione reductase and lower values of reduced glutathione were seen in the tumor as compared to those of the ventral prostate. Treatment with β-estradiol, an antiprostatic agent, does not seem to influence the growth or glutathione metabolism of squamous-cell carcinoma of the prostate. The observed changes in blood glutathione levels might prove to be useful as an index of rapid growth of the neoplastic tissue.
Subject
Cell Biology,Molecular Biology,Biochemistry,Biophysics
Reference32 articles.
1. Knox WE (1960) ?The Enzymes? (Boyer PD, Lardy H & Myrback K, eds), vol 2, pp 253?294, Academic Press, New York.
2. Isaacs J & Binkley F (1977) Glutathione dependent control of protein disulfide sulphydryl content by subcellular fractions of hepatic tissue. Biochim. Biophys. Acta497, 192?204.
3. Isaacs J & Binkley F (1977) Cyclic AMP dependent control of the rat hepatic glutathione disulfide sulphydryl ratio. Biochim. Biophys. Acta498, 29?38.
4. Chasseaud LF (1979) The role of glutathione and glutathione S-transferase in the metabolism of chemical carcinogens and other electrophilic agents. In ?Advances in Cancer Research? (Klein G & Weinhouse S, eds) vol 29, pp 176?255.
5. Hoekstra WG (1975) Biochemical function of selenium and its relation to vitamin E. Fed. Proc.34, 2083?2089.
Cited by
8 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献