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The Duration of the Myelotoxic Effects of Circulating Alkylating Agents

( Departments of Surgery, Sinai Hospital of Baltimore, Inc., and The Johns Hopkins University, School of Medicine, Baltimore, Maryland; and The Chemical Research Division, U. S. Army Chemical Research and Development Laboratories, Edgewood Arsenal, Maryland)

A technic has been devised to measure the active drug in circulating blood at various intervals after the intravenous injection of alkylating agents. The circulation to one hind leg (the protected leg) of a rabbit is blocked by tourniquet for varying periods of time during and after intravenous injection of an alkylating agent. After sacrifice of the rabbit (in 4 days) the bone marrows of the protected and unprotected legs are compared for changes in cellularity.

All the sulfur mustards tested, with the possible exception of S-170, disappeared rapidly from the circulation irrespective of their in vitro half-lives. Certain other alkylating agents such as bis-(1-aziridinyl)morpholinophosphine oxide and Sarcolysin did not follow this pattern. In these instances a toxic level was maintained in circulating blood for longer periods of time. The present study indicated that this technic may be useful for comparing agents with relatively long half-lives but not for comparison of agents with very short half-lives. It is probably more useful for predicting clinical behavior than is the in vitro half-life.

Received 5/21/64.