beta-carotene inhibits persistent and stimulates remodeling gamma GT-positive preneoplastic lesions during early promotion of hepatocarcinogenesis.

The inhibitory effects of beta-carotene or vitamin A on preneoplastic lesions induced in rats were compared, when specifically administered during early promotion of hepatocarcinogenesis. Initiation was performed by diethylnitrosamine. During the selection/promotion period 2-acetylaminofluorene was administered, and a partial hepatectomy was performed. Afterwards, the rats were divided into 3 groups. To two groups, beta-carotene or vitamin A were given for five weeks. Another group served as control and received corn oil. At the end of the study, beta-carotene reduced the incidence and total number of hepatocyte nodules. Vitamin A rats exhibited a lower number of nodules, but the incidence was 100%. Moreover, beta-carotene reduced the total number of gamma GT-positive preneoplastic lesions, as well as the morphometric parameters of persistent gamma GT-positive lesions. In contrast, morphometric parameters of persistent lesions remained almost unaffected in vitamin A animals. Furthermore, beta-carotene significantly increased the number of remodeling gamma GT-positive preneoplastic lesions. Vitamin A administration, however, resulted only in a small increase in the number of remodeling lesions. These results suggest that the inhibitory effects of beta-carotene during early promotion of hepatocarcinogenesis can be attributed not only to an inhibitory effect on persistent lesions, but also to a striking stimulatory activity on remodeling gamma GT-positive lesions.