Promoting Stage of Lung and Skin Carcinogenesis in Mice Carcinogenesis: Spontaneous Liver Carcinogenesis

Although B-carotene has been considered to be a key cancer preventive agent in green and yellow vegetables, other types of carotenoids, such as a-carotene, may also contribute to anticarcinogenic action, since these carotenoids usually coexist with/~-carotene and are detectable in human blood and tissues. In this study, we compared the inhibitory effect of natural a-carotene, obtained from palm oil, with that of B-carotene on spontaneous liver carcinogenesis in C3H/He male mice. The mean number of hepatomas per mouse was significantly decreased by a-carotene supplementation (per os administration in drinking water at a concentration of 0.05%, ad iibitum) as compared with that in the control group (P < 0.001, Student's t test). On the other hand, B-carotene, at the same dose as a-carotene, did not show any such significant difference from the control group. Furthermore, we also compared the antitumor-promoting activity of a-carotene with that of ~-carotene against two-stage mouse lung carcinogenesis (initiator, 4-nitroquinoline 1-oxide; promoter, glycerol), a-Carotene, but not E-carotene, reduced the number of lung tumors per mouse to about 30% of that in the control group (P < 0.001, Student's t test). The higher potency of the antitumor-promoting action of a-carotene compared to ~/-carotene was confirmed in other experimental systems; e.g., a-carotene was also found to have a stronger effect than E-carotene in suppressing the promoting activity of 12-O-tetradecanoylphorbol-13-acetate on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice. These results suggest that not only E-carotene, but also other types of carotenoids, such as a-carotene, may play an important role in cancer prevention. I N T R O D U C T I O N Epidemiological investigations have shown that cancer risk is inversely related to the consumpt ion of green and yellow vegetables (1-7). Since B-carotene presents in abundance in green and yellow vegetables and has the highest provi tamin A activity, B-carotene has been proposed as a key cancer preventive agent. In fact, experiments have confirmed that B-carotene prevented or delayed carcinogenesis induced by chemicals (8-10) and viruses (11). However, it should also be noted that B-carotene is often associated with other types of natural carotenoids, such as a-carotene, lycopene, etc. in daily foodstuffs (Table 1) (12). Fur thermore, not only B-carotene, but also these carotenoids, are detectable in human serum (13) and in a wide variety of tissues (14). Therefore, it is of interest to investigate the biological activity of these various kinds of carotenoids more extensively. Received 11/25/91; accepted 9/23/92. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. l Supported in part by grants from the Ministry of Education, Science, and Culture; the Smoking Research Foundation; and the Plant Science Research Foundation, Faculty of Agriculture, Kyoto University, Japan. 2 Present address: Oleochemistry Research Center, Lion Corporation, 7-13-12 Hirai, Edogawa-ku, Tokyo 132, Japan. To whom requests for reprints should be addressed. In recent studies, we found that a-carotene inhibited the proliferation of human mal ignant tumor cells more effectively than B-carotene (15, 16). In the present study, we further compared the activity of a-carotene with that of B-carotene against car-