A COMPARISON OF THE DESTRUCTIVE EFFECTS OF FIVE ANTITUMOUR AGENTS ON VARIOUS NORMAL TISSUES IN MICE

The destructive effects of N-formylsarcolysin (N-F), sarcolysin (S), endoxan (E), myleran (M), and 6-mercaptopurine (MP) on various normal tissues in mice were inves- tigated by quantitative histological methods. All the agents were given intraperitoneally at the dose levels of 1/5 and 1/15 LD₅₀ once daily for 5 consecutive days.Twenty-four hours after the last injection, the animals were sacrified and specimens from a variety of organs were taken for preparing histological sections. On the sections, the following cate- gories of tissue cells were counted: neutrophil granulocytes, eosinophil granulocytes, ery- thropoietic cells, and megakaryocytes in the bone marrow; lymphocytes in the thymus and the mesenterial lymph node; epithelial cells and Paneth cells in the crypts of Lieberkuhn of the small intestine; and spermatogonia of type A and type B in the testis. It was found that N-F and S may injure a wide range of tissues and changes occur in the bone marrow, thymus, lymph node, small intestine, and testis. The injuries of E and M on the bone marrow were comparatively more marked than those of N-F and S, while the injuries of E on the small intestine and of M on the lymph node were very slight. In addition, the destructive action of E on spermatogonia was less marked than that of N-F and S.The effects of MP were distinguishable from those of the above mentioned 4 alkylating agents by the following two points: (1) no detectable injury on spermatogonia and lymphocytes, and (2) less marked destruction on eosinophil granu- locytes. These results suggest that the differences of destructive effects on various normal tissues may occur not only between antimetabolites and alkylating agents but also among the various compounds belonging to the group of alkylating agents. The possible correlation between the destructive effect on normal tissue and the clinical anti-tumour effect of these agents was discussed.