Vitamin A and beta-carotene influence the level of benzo[a]pyrene-induced DNA adducts and DNA-repair activities in hamster tracheal epithelium in organ culture.
Although most studies concerning the effect of vitamin A and beta-carotene on chemical carcinogenesis are focused on tumour promotion and progression, these compounds may affect initiation as well. In this study the influence of vitamin A and beta-carotene on unscheduled DNA synthesis (UDS) was investigated in hamster tracheal epithelium in organ culture exposed to benzo[a]pyrene (B[a]P). DNA-repair activities were compared with the level of B[a]P-DNA adducts as measured both by 32P-postlabeling and by immunocytochemical detection. In hamster tracheal epithelial cells, both vitamin A and beta-carotene significantly increased B[a]P-induced UDS, with 40% and 45%, respectively. At the same time, vitamin A and beta-carotene decreased the level of B[a]P-DNA adducts in these cells with 18% and 40%, respectively as measured by 32P-postlabeling and with 12% and 35%, respectively as measured by immunocytochemistry. The effect of vitamin A on B[a]P-induced UDS and DNA-adduct levels in hamster tracheal epithelium appeared to depend on the dose of B[a]P vis-à-vis the concentration of vitamin A. The results of the present study show that both vitamin A and beta-carotene cause a decrease in B[a]P-DNA adduct levels by enhancing DNA-repair activities. Because the formation of B[a]P-DNA adducts is considered to be an early step in respiratory tract carcinogenesis, it is suggested that enhancement of DNA-repair activities by vitamin A and the subsequent removal of DNA adducts may be one of the mechanisms involved in vitamin A-mediated protection against cancer.
Wolterbeek
A P
AP
TNO Nutrition and Food Research Institute, Division of Toxicology, Zeist, The Netherlands.
Roggeband
R
R
van Moorsel
C J
CJ
Baan
R A
RA
Koeman
J H
JH
Feron
V J
VJ
Rutten
A A
AA
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002338:Carotenoids / Q000494:pharmacology*; D006224:Cricetinae; D018736:DNA Adducts; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects; D008647:Mesocricetus; D009924:Organ Culture Techniques; D014132:Trachea / Q000187:drug effects*; D014801:Vitamin A / Q000494:pharmacology*; D019207:beta Carotene
D018736:DNA Adducts; D019207:beta Carotene; D014801:Vitamin A; D001564:Benzo(a)pyrene; D002338:Carotenoids