On the Nature of Cancer 131 



Another group represented by 4-methoxy-6-nitrobenzotriazole arrests 

 only late, partially differentiated stages. The specificity in activity 

 is remarkable; even % hour of exposure to 0.1 ing./ml. of the quinoxa- 

 line brings about immediate arrest of the two-cell stage, whereas ex- 

 posure of 48 hours or more is required for arrest at the tail-bud stage. 

 Exposing two-cell stage embryos for as long as 30 hours to the same 

 concentration of the benzotriazole still permits development to the 

 blastula or early gastrula stage before death ensues. The selective 

 response to the quinoxaline appears to bear some relation to the 

 mitotic rate and resembles the response to radiation and to radio- 

 mimetic drugs. The benzotriazole effects, on the other hand, are 

 characterized by the absence of radiomimicry and by the heightened 

 sensitivity of the embryo with increasing age and with differentiation. 



These compounds illustrate the possibility of synthesizing compounds 

 which can selectively attack either growth or differentiation. The 

 finding of such compounds may be a matter of chance and perseverance, 

 since we cannot yet discern any relation between chemical structure 

 and function in this or any other series of compounds so far applied 

 to the problem. We have indicated not only the desirability but also 

 the practicability of such specificity in the chemotherapy of cancer. 

 If the cancer cell is a deficient mutant resulting from a virus infection, 

 then selective chemotherapy is within the grasp of the biochemist who 

 can pin-point the deficiencies and fashion drugs to exploit them. It 

 appears reasonable at this time to suggest that therapy be directed 

 toward energy-cycle mechanisms whether in the tumor or the host. 



Although the author alone is responsible for the ideas expressed 

 herein he owes a debt of gratitude to his associates, Ada M. Graff, 

 Morris Engelman, Horace B. Gillespie, and Kathe B. Liedke for carry- 

 ing out so much of the work from which these ideas are derived. The 

 author is also grateful to the Damon Runyon Memorial Fund, the 

 American Cancer Society, and the United States Public Health Service 

 for financial assistance in the prosecution of these researches. 



References 



1. L. C. Sze, J. Exptl. Zool, 122. 577 (1953). 



2. S. Graff and L. G. Barth, Cold Spring Harbor Symposia Quant. Biol., 6, 

 103 (1938). 



3. L. G. Barth and L. Jaeger, Physiol. Zool., 20, 133 (1947). 



4. J. P. Greenstein, The Biochemistry of Cancer, Academic Press, New York, 

 1947. 



