The proposed investigations are designed to determine if supplementation of the diet with vitamin A or Beta-carotene would result in inhibition of the incidence and development of salivary gland tumors. The effects of delayed administration of Beta-carotene and its mechanism of action as a cancer chemopreventive agent would also be studied. Tumors will be induced in submandibular salivary glands (SMSG) of rats by injecting dimethylbenzanthracene (DMBA) into one of the gland, the contralateral gland would be injected with the vehicle alone. During the initial experiments, rats will be fed diets supplemented with different levels of vitamin A and Beta-carotene. The dietary regimens will be initiated 4 weeks prior to the DMBA treatment and continued thereafter (20-24 weeks after the DMBA treatment). The incidence and weight of the tumors will be determined in each group along with its histological evaluation after hematoxylin and eosin staining. The activity of Gamma-glutamyltranspeptidase will be determined histochemically and biochemically in the SMSG (normal versus DMBA-treated) of rats fed different diets. Similar studies using DMBA-induced salivary gland tumor model, will also be conducted to determine if a delayed supplementation of the diet with Beta-carotene is effective in inhibiting tumorogenesis. The mechanism of cancer chemopreventive effects of Beta-carotene will be investigated by determining whether it is Beta-carotene per se or its ability to be converted to vitamin A in vivo is the main reason for its antitumor effects. These studies will include comparison of the chemopreventive ability of Beta-carotene with canthaxanthin, another C40 carotenoid which is not converted to vitamin A. Studies on the levels of tissue peroxides and Alpha-tocopherol as affected by Beta-carotene feeding will also be conducted in order to develop a better understanding of the mechanism of the tumor preventive effects of Beta-carotene.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE006893-03
Application #
3220386
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1984-03-01
Project End
1987-08-31
Budget Start
1986-03-01
Budget End
1987-08-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Type
School of Medicine & Dentistry
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Alam, B S; Alam, S Q; Bendich, A et al. (1989) Effect of dietary lipids on hepatic and plasma beta-carotene and vitamin A levels in rats fed beta-carotene. Nutr Cancer 12:57-60
Alam, B S; Alam, S Q; Weir Jr, J C (1988) Effects of excess vitamin A and canthaxanthin on salivary gland tumors. Nutr Cancer 11:233-41
Alam, B S; Alam, S Q (1987) The effect of different levels of dietary beta-carotene on DMBA-induced salivary gland tumors. Nutr Cancer 9:93-101
Alam, S Q; Alam, B S (1985) Microsomal fatty acid desaturase activities in vitamin A-deficient rat liver. Biochim Biophys Acta 833:175-7