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Inhibition of the Effects of Methylcholanthrene on Mouse Prostate in Organ Culture by Vitamin A and Its Analogs¹

Strangeways Research Laboratory, Wort's Causeway, Cambridge, England

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 (-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.

¹ This work was supported in part by funds from the Cancer Research Campaign (U. K.), and by Grants AM-05968 and HL-14236 (SCOR) from the NIH, Bethesda, Md.

² Sir Halley Stewart Fellow.

³ Permanent address: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, N. Y. This work was performed while Dr. Goodman was on leave from Columbia University as a Fellow of the John Simon Guggenheim Foundation.

Received 9/23/73. Accepted 3/20/74.

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