DEVELOPMENT OF EESISTANCE TO MERCURIALS 985 



Hg++ than the normal strains. Resistance to the mercurials is usually not 

 lost during subsequent culturing in mercurial-free media, as shown for fungi 

 (Partridge and Rich, 1962), yeast (Zambonelli, 1958 a), and spirochetes 

 (Launoy and Levaditi, 1913). The most striking case of the retention of 

 resistance is that of Salmonella, tolerance being unchanged during 55 trans- 

 fers over a period of 18 months (Severens and Tanner, 1945). It has thus 

 been concluded that the tolerance is inherited. Morphological changes dur- 

 ing adaptation generally do not occur, but yeast cells tolerant to Hg++ 

 are smaller, have lost their smooth contours, contain more vacuoles, and are 

 deficient in lipid (Imshenetsky and Perova, 1957). Growth of tolerant or- 

 ganisms in normal media is usually not different from that of sensitive 

 strains, and no instance of dependence on mercurials has been reported. 



Development of resistance to mercurials is not confined to microorgan- 

 isms but is observed in certain mammalian tissues. Gil y Gil (1924) claimed 

 to have produced renal tolerance to Hg++ in rabbits, but his work was 

 criticized by Hunter (1929), who repeated and extended this study using 

 more approijriate dosages. Rabbits given nephrotoxic doses of mercurial 

 exhibited a regeneration of the renal epithelium around the fourth day, 

 the new cells being elongated, flattened, with hyperchromatic nuclei, and 

 somewhat resistant to Hg++. Tsurumaki et al. (1928) confirmed that the 

 kidneys of rabbits surviving toxic injections of HgCl, are not damaged by 

 the same doses if given 10-14 days after the disappearance of the original 

 nephritis. During the period of adaptation, even though repeated subcutane- 

 ous injections are given, the nephritis disappears, but there is no alteration 

 in the excretion of Hg++ (Miura, 1934). MacNider (1941) repeated such ex- 

 periments in dogs and claimed that the newly regenerated renal epithelial 

 cells are different both morphologically and chemically from the normal 

 cells. The depressant effects of meralluride on intestinal transport of Na+, 

 CI", and water also disappear with repeated administration of the drug 

 (Blickenstaff, 1954), as does the suppression of conditioned reflexes in rats 

 given HgCL (Galoyan, 1957). 



