Showing papers by "DeWitt S. Goodman published in 1974"

Inhibition of the Effects of Methylcholanthrene on Mouse Prostate in Organ Culture by Vitamin A and Its Analogs

Abstract: Summary A study was conducted to examine in vitro the antagonism between the effects of a chemical carcinogen and four vitamin A-related compounds. The compounds studied included retinol, retinoic acid, and two analogs of retinoic acid (α-retinoic acid and a cyclopentyl analog, RO8-7699) with reduced or with virtually no growth-promoting vitamin A biological activity, respectively. Prostate glands of mice were grown in organ culture for 7 to 9 days. Methylcholanthrene (MCA) added to the culture medium stimulated the alveolar epithelium to become hyperplastic; such epithelium frequently displayed the first stages of squamous metaplasia or underwent parakeratosis. All four vitamin A-related compounds were highly active in inhibiting the effects of MCA. When added together with the carcinogen, the vitamin A compounds inhibited epithelial cell multiplication and maintained normal differentiation, thus counteracting the hyperplastic and metaplastic changes induced by MCA. Since all four compounds were highly active in antagonizing the effects of MCA, it is apparent that the anticarcinogenic activity of vitamin A is not correlated with the growth-promoting biological activity of the vitamin. Retinoic acid did not block the uptake of MCA by the mouse prostate gland or enhance its release from the gland. Addition of the detergent sodium dodecyl sulfate to the culture medium did not modify the effects of the carcinogen. This suggests that the effects of vitamin A are not due to its surface-active properties. The mechanisms involved in the antagonism of the vitamin A-related compounds and the carcinogen remain to be defined.

Vitamin A transport and retinol-binding protein metabolism.

Abstract: Publisher Summary This chapter elaborates the vitamin A transport and retinol-binding protein (RBP) metabolism. Vitamin A is a compound that exerts a number of important biological effects. In general, the vitamin is necessary for the support of growth and life of higher animals, since in the absence of vitamin A higher animals cease to grow, and in time die. Vitamin A is obtained in the diet either as the preformed vitamin or as a provitamin A compound such as β-carotene. In either case, retinyl esters are formed in the intestine and are absorbed into the body through the lymphatic pathway in association with lymph chylomicrons. The transport system for vitamin A in human plasma comprises two proteins, RBP and prealbumin. The techniques of circular dichroism and optical rotatory dispersion have been used to examine the effects of the interactions involved in retinol transport on the secondary structures of both RBP and prealbumin.