Binding of (chloroethyl 3H) cyclophosphamide to rat embryo proteins: two-dimensional gel analysis

Cells of the heart of the day 10 rat embryo are resistant to the cytotoxic effects of cyclophosphamide (CP) while cells of neuroepithelium (head) are sensitive. Using radiolabeled CP we have investigated the hypothesis that this difference in sensitivity is related to the binding (alkylation) of drug to specific proteins in heart and head cells. Two-dimensional gel analysis reveals that CP alkylates a variety of proteins in both heart and head cells. Although minor differences in the profiles of alkylated proteins exist between heart and head cells, the major proteins alkylated by CP in the two populations are identical. These data, therefore, do not support the hypothesis that sensitivity to the cytotoxic effects of CP is related to drug binding to specific proteins.