Studies on Colchicine, Colchicine Derivatives, and Endotoxin in Irradiated Animals

Colchicine when given 3, 2, or 1 day and trimethylcolchicinic acid methyl ether, colchiceinamide, colchiceine, and N-acetylcolchinol when given 1 day before irradiation caused an increase in survival of mice, provided they were more than 7 weeks old and the radiation dose one which causes death in approximately 1 to 4 weeks. Colchicine administration did not increase survival in irradiated rats, guinea pigs, and hamsters, although it caused mitotic arrest of marrow cells in each case. Mitotic inhibition was also evident in mice after a series of colchicine injections which abolished the effectiveness for survival of a single injection. Furthermore, in mice a much smaller dose of trimethylcolchicinic acid methyl ether inhibits mitosis than was required for increasing survival, although both effects were obtained with the same small dose of colchicine. These observations argue against the postulate that the effect on survival is mediaied through mitotic arrest. A variety of biological effects of endotoxin and colchicine are compared, including their effect on survival of irradiated mice of different ages and animals of different species, and granulocyte mobilization in animals of different species. These studies do not contribute positive evidence for or against a common pathway for the hemopoietic recovery inducedmore » by the two compounds. (auth)« less