756 6. ARSENICALS 



only 65% by 10 mM arsenite (Hockenhiill et al., 1954 b) and incubation 

 with arsenite leads to the accumulation mainly of a-ketoglutarate rather 

 than pjTuvate, indicating a somewhat different pattern of metabolism from 

 that in most organisms or tissues (HockenhuU et al., 1951). Although 1 

 mM arsenite interferes with the formation of itaconate from glucose in 

 Aspergillus terreus, mycelial weights increased almost 2-fold, perhaps 

 showing a diversion of pyruvate into cell material (Bentley and Thiessen, 

 1957). Only spore formation and not growth is blocked by arsenite in 

 Aspergillus niger, which is quite different from the results with most bacte- 

 ria. The sporulation of Venturia inequalis to produce infectious conidia 

 is likewise specifically inhibited by arsenite at 10-100 mM with respect 

 to growth, although the respiration is inhibited (Kirkham and Flood, 

 1963). The germination of Neurospora spores is 50% reduced by 1 mM 

 arsenite and completely by 10 mM (Sussman et al, 1958). The only con- 

 clusion that can be drawn from these heterogeneous observations, and the 

 metabolic effects discussed in other sections, is that the yeasts and fungi 

 are quite resistant to arsenicals, possibly due in part to the failure to pen- 

 etrate adequately into the cells. 



Viruses 



The multiplication of E. coli phage is inhibited completely by 0.6 mM 

 arsenite (Spizizen, 1943) and this effect is specific in the sense that phage 

 multiplication can be suppressed without a marked bacteriostatic action 

 (Dolby, 1955). Arsenite is one of the few inhibitors tested which possesses 

 this selectivity. It inhibits phage growth completely when added 15 min 

 after the latent period has begun, and partially inhibits after 22 min, indi- 

 cating a critical period for the effect. Oxophenarsine at 0.04 mM is also 

 capable of inhibiting coliphage multiplication without altering the growth 

 of the host cells (Czekalowski, 1952). However, at 0.4 mM it acts on both 

 phage and bacteria. Arsenite at 0.38 mM inhibits the proliferation of Co- 

 rynebacterium diphtheriae phage, but can convert an a virulent phage to 

 a virulent one (Hewitt, 1954). In one case, arsenite was effective in ridding 

 the bacteria of one of the lysogenic virus strains. The yield of foot-and- 

 mouth disease virus in cultures of pig kidney cells is reduced 90% by 0.05 

 mM arsenite, and completely by 0.1 mM, and this inhibition is not reversed 

 by the addition of succinate or glutamate (Planterose, 1961). There is thus 

 some evidence that arsenicals in the proper concentration range can selec- 

 tively suppress virus or phage proliferation, and it seems that this should 

 stimulate further work in the field, not only for the purpose of finding the 

 mechanism by which the arsenicals act but also to obtain information on 

 the factors involved in virus multiplication. 



