A study of the inhibition of tumor growth in mice and rats with 10-methyl-1,2-benzan-thracene and derivatives related to the nitrogen and sulfur beta-chloroethyl vesicants

T HE discovery of the lymphocidal activity"J, l1 of methyl-bis (8-chloroethyl) amine and tris (8-chloroethyl) amine was followed by the demonstration of definite palliative effects in chronic leukemia and Hodgkin's disease.ll.16, 22, 26 The specificity of action against neoplastic cells of these systemic poisons, as well as of the more toxics.l1' mustard gas (8-dichloroethyl sulfide) itself, is probably limited because of their rapid decomposition in body fluids'.12. l3.l4 and ready combination with cellular con~tituents.~The conclusion has been drawn from experiments with diethyl (8-iodoethyl) amine, containing radioactive iodine that cytotoxic effects were produced by a small fraction of the injected mustard, which was able to reach tumor cells before a reaction with blood constituents could O C C U ~, ~~, 24 and that the specificity of action against certain neoplasms was due more to the quantity of intact mustard able to reach the neoplasm than to any inherent specificity of action against these neoplastic cell~.~3,24In an attempt to confer a greater specificity of action against tumor on the 8-chloroethyl vesicants, substances were prepared that incorporated the mustard moiety into a carcinogenic hydrocarbon.One might expect not only that the hydrocarbon would confer greater lipophilic properties on the resulting