Neoplastic Growths 265 



oid tissue, excellent effects have been described. Colchicine ad- 

 ministered intravenously produced a sharp tall in temperature, which 

 in these patients is oltcn very high."-'' Substances chemically close to 

 colchicine but less toxic arc being tested; "methyl-colchicine" has 

 tjuite recenth j)i(ned to be ol \aluc in the management of cases of 

 chronic myeloid leukemia/'^ It is quite evident that it is too early to 

 draw a conclusion about the future o£ colchicine in cancer therapy, 

 and that far more Avork remains to be done. 



10.5: A Tool for the Study of Cancer Chemotherapy 



The mitotic stasis resulting from spindle destruction can make 

 visible small changes in the mitotic rate which would pass unnoticed 

 in microscopic sections (cf. Chapter 9) . Some promising work has 

 been initiated in this field. Urethane, at a dose of 0.5 gm/day, has 

 been demonstrated not to modify the number of mitoses, studied with 

 the colchicine method, in the Walker rat carcinoma 256.2' Azagua- 

 nine,**^- ''' on the other liand, has been proved to be one of the most 

 remarkable chemotherapeutic substances. This antagonist of guanine 

 and adenine can be demonstrated not to affect normal mitoses, while 

 strongly decreasing those of the BroAsn-Pearce carcinoma. This tumor 

 Avas studied Avhile grafted in the anterior chamber of the guinea pig's 

 eye.*"' This type of mitotic depression is made more evident by the use 

 of colchicine. 



Another type of experiment was planned for the study of an anti- 

 folic drug, aminoj^terine. Ihis substance is widelv used in the treat- 

 ment of acute leukemia, \\4ien large doses are injected into mice, 

 the cell divisions in the intestine do not take place any more for about 

 48 hours. During this period of mitotic inhibition, cellular and 

 nuclear groAvth are not impaired, and very large nuclei are formed. 

 When these divide again, the mitoses are of excejnional size. Colchi- 

 cine Avas used as a tool to arrest these mitoses and to provide a greater 

 number for study, as a consequence of the mitotic stasis. Also, the 

 shortening of the chromosomes made their counting easier, and ball 

 metaphases provided excellent material for photometric measure- 

 ments. These experiments indicated that the increase in nuclear size 

 was neither the result of polyploidv nor of polyteny.-'' 



10.6: Plant Tumors 



Whatever may be the exact relation between tumors in animals — 

 and. ill particular, cancerous growths — and the Aarious types of gall 

 formations induced in plants by Bacillus tumefacieus, insects, etc., it 

 is interesting to compare the effects obtained with colchicine with 

 those described for animal neoplasms. In a series of experiments on 

 Lycopersiciim escxdenlum inoculated with B. tumejaciens, a 1:10,000 



