Spontaneously transformed mouse fibroblasts
(Balblc 3T 12-3 cells) displayed an increased adhesion when
cultured in the presence of loF6 M all-trans retinol and acquired
morphological characteristics of the normal phenotype.
Thus it was of interest to investigate the metabolism
of [ 15-14C]retinol in this system. Within 24 hours of culture,
approximately 4.25% of the [14C]retinol was taken up by the
cells. The hydrocarbon [14C]anhydroretinol was a major
metabolic product and was identified by gas-liquid chromatography
and by its typical ultraviolet absorption spectrum
with maxima at 386, 364, and 346 nm. At 24 and 40 hours
anhydroretinol represented 27% and 55%, respectively, of
the total nonpolar metabolites or approximately 16% and
30% of the total radioactive products. Formalin-fixed fibroblasts
or cultured intestinal mucosal cells did not convert
retinol into anhydroretinol. A more polar product with a
UV absorption maximum at 310 nm was also found. The
time course of the synthesis of this product by 3T12 cells
suggested a precursor-product relationship with anhydroretinol.
A microsomal preparation from 3T 12 cells was also
active in synthesizing [14C]anhydroretinol and [14C]metabolite-
3 10 from [14C]retinol. Moreover incubation of metabolite-3 10
with the 3T12 microsomes yielded anhydroretinol(40% conversion
in 30 minutes), suggesting that metabolite-310 is an
intermediate in the synthesis of anhydroretinol by these cells.
Anhydroretinol appears to be an end product of the metabolism
of retinol in 3T12-3 cells, as suggested by the finding
that over 90% of [14C]anhydroretinoli ncubated for 30 hours
with 3T12-3 cells was recovered unaltered, without the formation
of detectable retroretinol, retinol, or retinoic acid.-
Bhat, P. V., L. M. De Luca, S. Adamo, I. Akalovsky, C. S.
Silverman-Jones, and G. L. Peck. Retinoid metabolism in
spontaneously transformed mouse fibroblasts (Balbk 3T12-3
cells): enzymatic conversion of retinol to anhydroretinol.
J . Lipid Re\. 1979. 20: 357-362