Uptake and metabolism of retinoic acid induces inhibition of cell growth: a study in a rat rhabdomyosarcoma cell line (BA-HAN-1C) using nonlinear theoretical models
Biesalski, H.K.; Brodda, K.; Gabbert, H.E.; Gerharz, C.D.; Engers, R.; Häussermann, B.; Koller, H.; Weiser, H.; Bässler, K.H.
International Journal for Vitamin and Nutrition Research. Internationale Zeitschrift für Vitamin- und Ernahrungsforschung. Journal International de Vitaminologie et de Nutrition 60(1): 4-18
1990
ISSN/ISBN: 0300-9831 PMID: 2387669 Document Number: 347941
Retinoic acid causes a significant inhibition of cell growth of the tumor cell line BA-HAN-1C. This growth inhibition is the same whether the cells are treated with a pulse dose of retinoic acid (RA) or continuously expand to RA. The determination of RA and its degradation products within the culture medium and in the cells showed that after 24 hours 13-cis-RA was the major retinoid in all cells (96 ng/10(6) cells); all-trans-RA represented 56 ng/10(6) cells. After 48 hours 4-hydroxy-RA and a small amount of 5,6-epoxy-RA was found in the cells and also in the culture medium. 4-hydroxy-RA increased up to 96 hours, whereas 13-cis- and all-trans-RA were not detectable in the cells after 96 hours. We conclude that the BA-HAN-1C cells take up and metabolize RA. Nonlinear fit analysis of the time behavior of the RA concentration in medium demonstrates that the RA uptake unexpectedly follows a mono-exponential time function. Discussion of the experimental results in connection with a proper compartment model shows that uptake and metabolism of RA cannot be described really by a first order kinetics. The mathematical analysis leads to a more complicated kinetic model with certain restrictions for the corresponding rate constants.