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ß-Carotene and Aryl Hydrocarbon Hydroxylase in the Rat: An Effect of ß-Carotene Independent of Vitamin A Activity^1,2,

Thomas E. Edes^*,, William Thornton, Jr.^* and Jayendra Shah^*,

^* Department of Medicine, Harry S. Truman Memorial Veterans Hospital University of Missouri Medical Center, Columbia, MO 65201

Animal models demonstrate a cancer-protective effect of vitamin A. However, human epidemiologic studies correlate the intake of the precursor, ß-carotene, rather than active vitamin A, to a reduced risk for certain cancers. This suggests that ß-carotene may have cancer-protective properties independent of its vitamin A activity. In the present rat study, effects of ß-carotene or active vitamin A on carcinogen metabolizing enzyme activity were evaluated. The activity of intestinal aryl hydrocarbon hydroxylase (AHH, EC 1.14.14.1) was higher in rats fed a purified diet supplemented with ß-carotene than in rats fed the control diet containing adequate vitamin A as retinyl palmitate (165 ± 30 vs. 90 ± 18 pmol/min x mg), P < (0.05). Supplementing the control diet with retinyl acetate had no effect. This AHH-enhancing effect of ß-carotene on the activity of the intestinal mucosal enzyme was not seen on the hepatic enzyme, which is consistent with the nearly complete conversion of ß-carotene to vitamin A prior to reaching the liver. These results demonstrate an effect of ß-carotene on carcinogen metabolism which is independent of its vitamin A activity. This may help explain human epidemiologic data, and may lead to further work which would allow for prudent dietary recommendations toward a reduction in cancer risk.

KEY WORDS: • ß-carotene • vitamin A • carcinogen • benzo()pyrene metabolism • aryl hydrocarbon hydroxylase

¹ Supported by the Veterans Administration.

² Presented in part at the 72nd Annual Meeting of the Federation of American Societies for Experimental Biology, Las Vegas, NV, May 3, 1988. FASEB J. 2: 3281, 1988.

Manuscript received 21 November 1988. Revision accepted 6 February 1989.