Uptake and metabolism of β-carotene and retinal by C3H/10T1/2 cells

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Abstract
Both β-carotene (β-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 β-C in these cells may be attributed to conversion to vitamin A or is intrinsic to the carotenoid molecule, the uptake and metabolism of β-C, and of retinal, the immediate product of dioxygenase-cleavage of β-C, was studied in 10T1/2 cells. Cellular uptake of 2.6 nmol/106 cells occurred 24h after treatment with 10−5 M β-C. Thereafter, cell levels remained relatively stable between 1 and 2 nmol/106 cells over the 1-week treatment period. Upon removal of β-C from the medium, cellular levels decreased by ˜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 β-C to retinal by these cells would be expected to result in retinol as the end product. Using [14C]β-C, we found no evidence for formation of [14C]retinol, [14C]retinal or [14C]retinoic acid using sensitive HPLC. We therefore conclude that β-C has intrinsic chemopreventive activity in 10T1/2 cells, perhaps due to its anti-oxidant properties.