440 ROLLIN D. HOTCHKISS 



producing genie mutations in fungi^* and corn -^ were shown to be equiva- 

 lent to an ultraviolet absorption curve of nucleic acid. The specificity of 

 this indication is not great enough to show unquestionably that protein is 

 not absorbing the effective quanta, and mutagenic action is indeed con- 

 siderable at the absorption maximum for protein. Furthermore, even 

 though the ultraviolet energy may have been absorbed by nucleic acid or 

 nucleoprotein, activated molecules or atoms may then have produced the 

 ultimate significant chemical changes at some site other than the nucleic 

 acid itself. These conceptions, and the recognition that added substances 

 and environmental factors could considerably modify the number of 

 mutations detected after ultraviolet irradiation, tended to prevent any 

 general acceptance of this phenomenon as an indication of the chemical 

 nature of genes. More recently, the possibility of reversing ultraviolet 

 mutational and lethal effects by subsequent exposure to visible light" -^^ 

 (photoreactivation) as much as three hours later has emphasized that 

 mutagenesis by this agency is an indirect and certainly not a simple pro- 

 cess. Nevertheless, the known facts fit well with a genetic role for DNA. 

 Prolonged ultraviolet irradiation of high-molecular calf thymus DNA can 

 bring about structural changes interpretable as depolymerization.^' Treat- 

 ment of Escherichia coli with low doses of ultraviolet inhibits DNA synthe- 

 sis in these bacteria without appreciably affecting respiration or PNA 

 synthesis, and does this before an effect upon growth is apparent.^* 



Some evidences of the chemical nature, or at least reactivity, of gene 

 material can be found in the demonstrated chemical effects of certain 

 other mutagenic agents. Sulfur mustard probably was the first chemical 

 substance clearly shown to induce mutations." On the basis of the kinetics 

 of inactivation by sulfur mustard of a diverse series of biological materials 

 ranging from pure protein enzymes to several viruses, bacteria, and yeast, 

 Herriott concluded that DNA was a much more sensitive component of 

 living cells than protein or PNA.-^ This conclusion, arrived at by biological 

 test, seems significant in view of the numerous reports that sulfur and 

 nitrogen mustards can produce mutations in a number of species. The 

 demonstration that these substances can react chemically with DNA has 



1^ A. Hollaender and C. W. Emmons, Cold Spring Harbor Symposia Quant. Biol. 9, 



179 (1941). 

 «» L. J. Stadler and F. M. Uber, Genetics 27, 84 (1942). 

 " A. Kelner, J. Bacteriol. 58, 511 (1949). 



22 A. Novick and L. Szilard, Proc. Natl. Acad. Sci. U.S. 35, 591 (1949). 



23 A. Hollaender, J. P. Greenstein, and W. V. Jenrette, /. Natl. Cancer Inst. 2, 23 

 (1941). 



24 A. Kelner, /. Bacteriol. 65, 252 (1953). 



25 C. Auerbach and J. M. Robson, Nature 157, 302 (1946). 

 2« R. M. Herriott, J. Gen. Physiol. 32, 221 (1948). 



