Uptake and metabolism of {beta}-carotene and retinal by C3H/10T1/2 cells

Both ß-carotene (ß-C), a vitamin A precursor,and vitamin A itself have been shown to reversibly inhibit neoplastictransformation in 10T1/2 cells during the progression phaseof carcinogenesis. In order to determine whether the activityof ß-C in these cells may be attributed to conversionto vitamin A or is intrinsic to the carotenoid molecule, theuptake and metabolism of ß-C, and of retinal, theimmediate product of dioxygenase-cleavage of ß-C,was studied in 10T1/2 cells. Cellular uptake of 2.6 nmol/10⁶cells occurred 24h after treatment with 10^–5 M ß-C.Thereafter, cell levels remained relatively stable between 1and 2 nmol/10⁶ cells over the 1-week treatment period. Uponremoval of ß-C from the medium, cellular levels decreasedby {small tilde}80% in 2 weeks, then stabilized. Retinal wasrapidly and quantitatively converted to retinol by 10T1/2 cells,suggesting that the inhibitory action of retinal on neoplastictransformation in these cells is due to its conversion to retinol,and that any enzymatic conversion of ß-C to retinalby these cells would be expected to result in retinol as theend product. Using [¹⁴C]ß-C, we found no evidencefor formation of [¹⁴C]retinol, [¹⁴C]retinal or [¹⁴C]retinoicacid using sensitive HPLC. We therefore conclude that ß-Chas intrinsic chemopreventive activity in 10T1/2 cells, perhapsdue to its anti-oxidant properties.