Carrier-dependent and carrier-independent transport of anti-cancer alkylating agents

While it is understandable that proliferating cells should be more sensitive than resting cells to antimetabolites—drugs that derange DNA synthesis—it is not so obvious that other anti-cancer drugs, in particular the alkylating agents, should act in the same way 1–3 . The greater sensitivity of proliferating cells to such agents is not confined to malignant tissues: normal haematopoietic cells show increased susceptibility after recruitment into cell division 4 . Moreover, the various alkylating agents have different effects on proliferating nonmalignant cells; in normal bone marrow, recovery is more rapid 5 and greater 6 after treatment with some drugs (for example, cyclophosphamide and nitrogen mustard) than others (such as nitrosoureas and mitomycin C). We now provide evidence in support of the hypothesis that there are two distinct groups of alkylating agent: those whose uptake into the cell depends on a membrane transport mechanism (that is, carrier-dependent) and those whose uptake is not so dependent (carrier-independent).