During an investigation of the effect of the carcinoclastic compound, podophyllotoxin, on tissue respiration, we observed that injection of this compound into normal rats produced marked reduction of the respiration of spleen, lymph node, and thymus gland slices (1). Lymphatic tissue appeared to be particularly sensitive to podophyllotoxin, in sharp contrast to liver and kidney, which were not inhibited. This selective inhibition was dearly demonstrable only when the compound was injected into animals. The reduction of lymphatic tissue respiration when podophyllotoxin was added in vitro was not strikingly different from that of liver or kidney (2).In order to determine whether this effect on lymphatic tissue is a unique property of podophyllotoxin or is common to other carcinoclastic agents, we have compared the activity of podophyllotoxin in this respect with three compounds of widely differing chemical structure, which have, nevertheless, the common property of inhibiting the growth of certain types of tumors. In this paper we present the results of experiments in which colchicine, urethane, and one of the nitrogen mustards, methyl-bis(fl-chloroethyl)amine, have been compared with podophyllotoxin. These three compounds were chosen because, like podophyllotoxin, (1) they possess carcinoclastic properties; (2) they inhibit cell mitosis; (3) they depress hematopoietic activity (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Moreover, they have the common property of provoking what Dustin (21) has called the "crise caryoclasique," the crisis of nuclear fragmentation, in the lymphoid system and thymus.Published work on the effect of the compounds on tissue respiration is rather meager. In 1934 Lits first reported that colchicine inhibited the division of animal cells at metaphase (22). In the enormous body of literature on colchicine, comprising
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