Concentration and Time-dependent Inter-relationships for Cytotoxicities of Nitrogen Mustard Drugs against Lymphoblasts In-vitro

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Abstract
Peripheral lymphoblasts were exposed either to different initial concentrations of the alkylating agents (melphalan, chlorambucil or phenylacetic acid mustard) using a fixed incubation time or a constant initial concentration with variable exposure times. The cytotoxic activity was evaluated as the inhibition of [3H]methylthymidine incorporation into the trichloroacetic acid-insoluble fraction of the cells. The concentration-time relationships were evaluated by calculating the amount of drug which had chemically reacted in the incubation system. Melphalan showed lower cytotoxicity at short exposure times and high drug concentrations, while chlorambucil exhibited higher cytotoxicity at longer exposure times. In the latter case the effect could be accounted for by the cytotoxic activity of monohydroxy chlorambucil which was formed in the incubation system.