Antitumor activity in skin of Skh and Sencar mice by two dietary beta-carotene formulations.
There is currently a great interest in the protective potential of beta-carotene and other micronutrients against carcinogenesis. We investigated the role of beta-carotene in modifying 7,12-dimethylbenz[a]anthracene (DMBA)-initiated, 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted, two-stage skin carcinogenesis. We were interested in comparing the protective effects of two types of dietary beta-carotene, a beadlet formulation and crystalline beta-carotene, in two strains of mice (Skh:HR-1 and CR:ORL Sencar). Mice were maintained throughout the study on one of these 3% beta-carotene-fortified diets or on control diets. In Week 11 after the start of the diets, the DMBA/TPA treatment regimen was begun. The resulting skin tumors were counted weekly. In addition, serum and skin levels were monitored for beta-carotene at the time of chemical initiation and at the termination of the study. A decrease in the number of cumulative tumors in the beta-carotene-fed animals compared with the appropriate control groups was observed in both strains of mice. However, statistical evaluation of the data revealed that the decrease was significant only in Skh mice. This phenomenon might be explained by the inherent sensitivity of Sencar mice to the two-stage carcinogenesis treatment regimen. The mechanism of the protective effect found in this study is still not clear. Recent data suggest that a vitamin A pathway is not probable but that a direct 1O2 and/or radical-quenching property of the parent beta-carotene molecule may be involved. This study also demonstrates that two-stage-induced skin tumorigenesis can be modified by both types of beta-carotene-fortified diets.
Lambert
L A
LA
Division of Toxicology, US Food and Drug Administration, Washington, DC 20204.
Koch
W H
WH
Wamer
W G
WG
Kornhauser
A
A
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001835:Body Weight; D002338:Carotenoids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004032:Diet; D005260:Female; D005527:Food, Fortified; D051379:Mice; D008815:Mice, Inbred Strains; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives; D019207:beta Carotene
D019207:beta Carotene; D002338:Carotenoids; D015127:9,10-Dimethyl-1,2-benzanthracene; C032975:12-O-tetradeca-2,4,6,8-tetranoylphorbol-13-acetate; D013755:Tetradecanoylphorbol Acetate