764 6. AKSENICALS 



were changed (since the work was done with cell suspensions). Williamson 

 felt tnat triose utilization bypassed the 3-phosphoglyceraldehyde dehydro- 

 genase step, which he assumed to be sensitive to the arsenicals; also that 

 the disappearance of the pyruvate system might indicate a shift of the 

 metabolism. Reliable interpretation cannot be made until quantitative 

 work is carried out on enzymes obtained from normals and resistants. 



We may next inquire if there are changes in the biological properties 

 of resistant organisms. Marks (1910) produced the first arsenical-resistant 

 bacteria by culturing Salmonella with arsenite, and found that they become 

 immotile, acquire a thicker shape, lose some flagella, and are altered in 

 certain growth and culture characteristics, such as color. Resistant organisms 

 show no particular change in virulence (Voegtlin et al., 1924). However, 

 some change in the immune response of the host was noted by Tobie and 

 von Brand (1953), in that animals infected with a resistant strain survive 

 significantly longer than with a normal strain, the survival time often being 

 doubled. A change in agglutination properties also occurs; an oxophenarsine- 

 resistant trypanosome showed a marked tendency to agglutinate when 

 infected blood was diluted with physiological saline, although the cells 

 remained motile (Cantrell, 1955). However, some other highly resistant 

 strains were nonagglutinating, so that the two properties do not necessarily 

 go together. 



Resistance in Higher Animals 



Ignoring the Styrian arsenic eaters, whose problems are not directly 

 pertinent to our subject, one finds that a low degree of tolerance may be 

 produced occasionally in the higher animals, but many failures have also 

 been reported. Morishima (1900 a) could not induce resistance to arsenite 

 in rabbits following multiple administrations, and Bucher (1950) was 

 unable to show resistance in tissue cultures after 4 months of treatment 

 with arsenite. It should be noted that arsenite has been used in most mam- 

 malian work and this form of arsenic has never been found to produce 



