540 5. QUINONES 



stituted quinones injected intraperitoneally twice daily in Twort carcinoma- 

 bearing mice for approximately 2 weeks canse an inhibition of the tumor 

 growth (see accompanying tabulation) (Powell, 1944). The animals gain 



^ . Dose Interval „ r^, .,.,.. 



Quinone , ^ , , ^ % Tumor inhibition 



(mg) (days) 



weight during this period, indicating a specific effect on the tumor tissue. 

 The feeding of 9,10-PAQ at 1-2% in the diet to mice inhibits the growth 

 of Carcinoma 63, and a fibrosarcoma is inhibited even more; indeed, oc- 

 casional complete regression was observed (Powell, 1951). Adenocarci- 

 nomas, squamous cell carcinomas, sarcomas, and a spindle-cell tumor are 

 also inhibited. Powell observed some reaction of these substances with pro- 

 teins and believed that reaction with SH groups might be important. It is 

 very difficult, as previously discussed, to be certain that the activity is 

 associated with the quinone structure when the polycyclic compounds are 

 used, since nonquinonoid analogs or similarly substituted saturated hydro- 

 carbons are not used as controls. The uptake of these quinones by tumor 

 tissue is well shown in the work of Lewis and Goland (1947), who found 

 that after 16 days the tumors in mice fed 0.25% l,4-diamino-9,10-AQ 

 are reduced to one fourth the original size and are stained purple. Sakai 

 et at. (1955) found that intraperitoneal injections of 10-20 mg/kg/day of 

 2-methylthio-l,4-NQ or 2,3-dimethylthio-l,4-NQ prolong the lives of mice 

 inoculated with Ehrlich ascites carcinoma cells, and felt that the methyl- 

 thio derivatives give the best promise for suppression of tumors in vivo. 

 Fukuoka et al. (1957) suggested that these carcinostatic quinones suppress 

 tumor growth through an inhibition of glycolysis because of a close cor- 

 relation of the two activities. On the other hand, quinones have been 

 found to stimulate tumor growth. Badger et al. (1942) observed an increase 

 in the size of implanted Walker rat carcinoma 256 during the administra- 

 tion of 1,4-naphthoquinone and menadione. It is interesting to note that 

 duroquinone at rather high doses had no effect on the tumor growth; there 

 has been very little study of the benzoquinones in this connection. 



The most intensive investigation of this subject has been made by the 

 group at Cambridge in relation to the general problem of the antimitotic 



