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.
Rizzi
M B
MB
Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Brazil.
Dagli
M L
ML
Jordão
A A
AA
Penteado
M V
MV
Moreno
F S
FS
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D004224:Diterpenes; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control; D008297:Male; D011230:Precancerous Conditions / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D000084562:Retinyl Esters; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D019207:beta Carotene / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D005723:gamma-Glutamyltransferase / Q000032:analysis*
D016588:Anticarcinogenic Agents; D004224:Diterpenes; D000084562:Retinyl Esters; D019207:beta Carotene; D014801:Vitamin A; C014794:retinol palmitate; D005723:gamma-Glutamyltransferase