ANALOGS OF PYEIDOXAL 577 



mice, with a specific regression of the tumor and no weight loss (Shapiro 

 and Gellhorn, 1951). Human carcinoma cells (Eagle's KB strain) are quite 

 sensitive to deoxypyridoxol in tissue culture, 0.08 mM inhibiting the growth 

 50% (Smith etal., 1959). It appears doubtful that deoxypyridoxol is suffi- 

 ciently specific as a carcinostatic agent but its use in conjunction with other 

 inhibitors remains a possibility, especially as Doctor (1959) has shown that 

 deoxypyridoxol at 20 mg/kg/day in the rat has no effect on the leucocyte 

 count, but combined with a moderately effective dose of aminopterin exerts 

 a very marked suppression of the leucocytes, and also potentiates the action 

 of oxythiamine. 



Toxic Effects in Whole Animals 



Some of the evidence that deoxypyridoxol can produce rather typical 

 vitamin Bg-deficiency states will be summarized to emphasize that, what- 

 ever the basic biochemical disturbances, the effects are primarily related to 

 an interference with formation or function of pyridoxal-P. It is first of all 

 quite clear that the doses of deoxypyridoxol to induce toxic reactions must 

 be much higher when the animals are adequately supplied with the Bg vi- 

 tamers than when the animals are subjected to a dietary deficiency, and 

 that administration of pjTidoxol can overcome the toxic reactions produced 

 by the analog. In general the responses to deoxypyridoxol are the same 

 as in pyridoxine deficiency, except that they appear earlier, producing an 

 acute deficiency syndrome. Thus in rats and mice there is a dermatitis 

 characterized by acanthosis, parakeratosis, and hyperkeratosis, sometimes 

 with a superimposed infection, which is similar to deficiency dermatitis 

 (Stoerk, 1950). There is atrophy and degeneration of the hematopoietic 

 organs, evidenced by decreases in thymus and spleen weights, and these are 

 reflected in the peripheral blood picture (Mushett et al., 1947). The nervous 

 system hyperirritability leading eventually to convulsions has been men- 

 tioned in connection with the metabolic changes in the brain. 



A state resembling pyridoxine deficiency has been produced in man by 

 Mueller and Vilter (1950). Eight individuals on a pyridoxine-poor diet were 

 injected intramuscularly with 60-150 mg/day. Within 2-3 weeks a sebor- 

 rheic dermatitis appeared around the eyes, nose, and mouth, with simulta- 

 neous glossitis and stomatitis. These symptoms disappeared in 2-3 days 

 upon administration of pyridoxol. The total white count did not fall, nor 

 was there evidence of anemia, but the lymphocytes dropped to around half 

 the initial level. Schrodt et al. (1960) in their two carcinoid patients also 

 observed seborrheic dermatitis and glossitis. The general pharmacology of 

 analogs and inhibitors of pyridoxal function has been reviewed by Holtz 

 and Palm (1964). 



Although several workers have stated that reactions may be seen in acute 

 deoxypyridoxol-treated animals which are not seen in simple dietary de- 



