In Vitro Cytotoxic Effects of Dibromodulcitol in 9L Rat Brain Tumor Cells.

Dibromodulcitol (DBD) is a halogenated hexitol active against animal and human brain tumors in vivo. In aqueous solution, DBD is transformed to products with different cytotoxicities. We studied the in vitro activation and inactivation of DBD with a bioassay in 9L rat brain tumor cells. We developed a mathematical model to calculate the rate constants of activation and inactivation. The kinetics of the activation and inactivation of DBD transformation products in cell culture medium were exponential, with rate constants of 0.139 and 0.0189 hr(-1), respectively. The maximum cell kill was caused by DBD that had been preincubated in medium for 13-16 hr. Thus cell kill is not caused by parent drug but by active transformation products.