A serum oestradiol/4-hydroxyestradiol ratio test as prostatic tumour marker.
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Biomedical subjects
Publications and source records attributed to L B Nieuwoudt.
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The 2-hydroxy and 4-hydroxyestradiols (2-/4-OHE2) caused marked cytotoxic effects, including vacuolation and nuclear changes, in rat epididymal epithelia, after exposure to very low levels (40 ng/rat/week) for 20 weeks. The effects of the 2-/4-OHE2 metabolites were more pronounced than that of estradiol-17 beta (E2).
Various authors have demonstrated that estrogens stimulate both protein and DNA synthesis, as well as cell proliferation. This study was therefore undertaken to investigate the correlation between these physiological effects of estrogens and the total prostatic catecholestrogens. Either 17 beta-estradiol (5 ng), 2-hydroxyestradiol (40 ng), 4-hydroxyestradiol (17 ng), propane-1,2-diol or a saline solution was injected intraperitoneally to 22-day-old Sprague-Dawley rats daily. Regardless of the treatment, the prostate mass, the rate of DNA or protein synthesis correlates positively with the total prostatic catecholestrogen concentration. We therefore conclude that the effect of each estrogen per se should be regarded in terms of the total prostatic catecholestrogen concentration.
Estradiol and other estrogens are not classified as genotoxic carcinogens, but rather as tumor promoters in the multistage process of carcinogenesis. This study is a reexamination of the carcinogenic status of estradiol and the catecholestradiols (2-OHE2 and 4-OHE2) with the recently developed bacterial assays for genotoxic carcinogens, the Chromotest. The bacterial kits revealed estradiol and catecholestradiols as biphasic and potential genotoxic carcinogens with the following SOS inducing potency values: E2 43,265 (SD 8,300); 2-OHE2 30,153 (SD 2,500), and 4-OHE2 68,939 (SD 4,500). The differences between these values are statistically highly significant (p less than 0.0005). These results were confirmed by studies on Escherichia coli, which showed an increase in cell number and a stimulation of DNA content in the presence of the estrogens. It is therefore concluded that estradiol and the catecholestradiols are possible genotoxic carcinogens which probably act as tumor inducers rather than tumor promoters.