516 5. QUINONES 



readily post-mortem in the blood of poisoned animals. The formation of 

 methemoglobin in vitro by the quinones is catalytic, as shown by the very 

 low minimal concentrations necessary — durohydroquinone (0.00028 mM), 

 p-benzohydroquinone (0.061 mM), menadione (0.00063 milf), 3-methyl- 

 menadione (0.0054 mM), and 2-ethyl-l,4-naphthoquinone (0.00054 mM) — 

 the quinones being reduced by various reactions in the erythrocytes (From- 

 herz, 1941). The relation of the formation of methemoglobin to the effects 

 of the quinones on erythrocyte respiration have been discussed previously 

 (page 489). The rates at which methemoglobin is formed in dog blood 

 incubated with various quinones were determined by Hoffm.ann-Ostenhof 

 et al. (1947 a), who felt there to be no relationship to redox potential 

 or the inhibition of any enzymes (see accompanying tabulation). The 



^ . Methemoglobin formation E,^' (pH 7) 



^"•"""^ (mg/100 ml/hr) (v) 



lack of a general correlation with redox potential may be due to various 

 factors, but it would be difficult to evaluate these without information on 

 the relative rates of the direct oxidation of hemoglobin. In any event, one 

 must assume that hemoglobin, along with numerous other substances in 

 the blood, is able to reduce quinones and hence possibly alter their toxicity, 

 as Liu (1928) suggested. 



The chronic administration of p-benzoquinone, menadione, and phthiocol 

 brings about rather marked falls in erythrocytes and hemoglobin, agranulo- 

 cytosis, and often pancytopenia (Kracke and Parker, 1934; Molitor and 

 Robinson, 1940; Ansbacher et al, 1942; Jung and Witt, 1947). Since the 

 quinones are antimitotic one might expect a depression of the hematopoietic 

 tissues. In most instances it requires 2-4 weeks for hematopoietic depres- 

 sion to be manifest and it often occurs with quite small doses, e, g., 15 mg/ 

 day of 2)-benzoquinone injected into rabbits. Some of the erythrocyte and 

 hemoglobin reduction may be the result of hemolysis; indeed, where this 



