Uptake and metabolism of beta-carotene and retinal by C3H/10T1/2 cells.
Both beta-carotene (beta-C), a vitamin A precursor, and vitamin A itself have been shown to reversibly inhibit neoplastic transformation in 10T1/2 cells during the progression phase of carcinogenesis. In order to determine whether the activity of beta-C in these cells may be attributed to conversion to vitamin A or is intrinsic to the carotenoid molecule, the uptake and metabolism of beta-C, and of retinal, the immediate product of dioxygenase-cleavage of beta-C, was studied in 10T1/2 cells. Cellular uptake of 2.6 nmol/10(6) cells occurred 24 h after treatment with 10(-5) M beta-C. Thereafter, cell levels remained relatively stable between 1 and 2 nmol/10(6) cells over the 1-week treatment period. Upon removal of beta-C from the medium, cellular levels decreased by approximately 80% in 2 weeks, then stabilized. Retinal was rapidly and quantitatively converted to retinol by 10T1/2 cells, suggesting that the inhibitory action of retinal on neoplastic transformation in these cells is due to its conversion to retinol, and that any enzymatic conversion of beta-C to retinal by these cells would be expected to result in retinol as the end product. Using [14C]beta-C, we found no evidence for formation of [14C]retinol, [14C]retinal or [14C]retinoic acid using sensitive HPLC. We therefore conclude that beta-C has intrinsic chemopreventive activity in 10T1/2 cells, perhaps due to its anti-oxidant properties.
Rundhaug
J E
JE
Basic Science Unit, University of Hawaii, Honolulu 96813.
Pung
A
A
Read
C M
CM
Bertram
J S
JS
D000818:Animals; D001692:Biological Transport; D001711:Biotransformation; D002338:Carotenoids / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D051379:Mice; D012172:Retinaldehyde / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism*; D013997:Time Factors; D014801:Vitamin A / Q000378:metabolism; D019207:beta Carotene
D012176:Retinoids; D019207:beta Carotene; D014801:Vitamin A; D002338:Carotenoids; D012172:Retinaldehyde