We reported previously the carcinostatic action of cholesterol-3-methylether and estradiol-3-methylether on Ehrlich ascites cancer(solid form and ascites form), NF sarcoma and some kind of human cancer.
To clarify whether the anticancer action of cholesterol-3-methylether results from metabolic antagonism -of steroid through the substitution of -OCHs for its -3-0H or not, we performed following experiments. 1) The influence of cholesterol-3-methylether on the modified Thorn test in mice.
2) The influence of cholesterol-3-methylether on the blood sugar level in starved rabbits. 3) Urinary excretion of 17-ketosteroids, 17-hydroxycor ticosteroids and chemocorticoids after the admistration of cholesterol-3-methylether to mice, rats and patients with malignant tumors.
4) Experimental verification of radioactive C14 in urinary 17-ketosteroids fraction after injection of cholesterol-4-C14-3-methylether in rabbits.
5) Experimental verification of OCH3 group in urine and urinary 17-ketosteroids fraction by administration of cholesterol-3-methylether in rats, normal human and cancer patients.
Mice were injected with cholesterol or cholestrol-3methylether and ACTH simultaneously to see how to influence over the adrenocortical function in accordance with modified Thorn test. In animals receiving cholesterol-ACTH, circulating eosinophiles decreased considerably as would be expected, but with cholesterol-3methylether-ACTH, there was no decrease but` to_ the contrary an increase occurred.
Starved rabbits were administered cholesterol-3-methylether intramuscularly to -observe change of blood sugar level to see how to influence on the adrenocortical function indirectly, by Folin-Wu´s method. In rabbits administered cholesterol-3-methylether, blood sugar level declined more early than nontreated starved rabbits. Cholestrol-3-methylether possibly causes an altered function of adrenocortex.
Colorimetric study of the urine of mice and rats administered cholestrol-3-methylether revealed abnormally large amount of chemocorticoids, 17hydroxycorticoids, and 17-ketosteroids. And same study was performed for malignant tumor patients and found same results as in animals.
Qualitative determination of methoxy molecule in the urine of rats and human administered cholesterol-3methylether intramuscularly was performed by MicroZeisel´s method, and we found methoxy group considerably in those urines. Then same survey was done on the steroid fraction of rabbit´s urine. After administration of cholesterol-3-methylether. to rabbits intramuscularly, urinary 17-ketosteroid was separated chromatographically by Pincus method. And in the eluted 17-ketosteroids fraction methoxy molecule was noticed in the same way.
The results demonstrated that a large quantity of methoxy substituted 17-ketosteroids were excreated in the urine of animals administered cholesterol-3-methylether. The methoxy substituted steroids could be said consequently not to act as normal steroids
For further confirmation cholesterol-4-C14-3-methylether was used and considerable. Counts of C14 in the chromatographically separated .17-ketosteroid fraction was found. That is, in case #I, administered 417. 060 counts of cholesterol-4-C-14-3-methylether, .found 330 counts(0. 079%) from urinary 17-ketosteroid fraction for I week -.in rabbits, in case #2 administered 139,020 counts, found 50 counts(0.036%), in case #3, administered 837, 480 counts, found 132 counts(0, 016%), in case #4, administered 837, 480 counts, found 56 counts (0,007%).
In summary it can be stated that an analogue of cholesterol is metabolized but it interfere with the production of normal adrenal corticoid and 17-ketostero ids.
It is postulated that this analogue has an antagonistic fiction on steroid metabolism.
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