Accession Number : AD0714158

Title :   Studies on Drug-Induced Immunological Tolerance.

Descriptive Note : Final rept. 1 Mar 69-30 Jun 70,

Corporate Author : COLLABORATIVE RESEARCH INC WALTHAM MASS

Personal Author(s) : Friedman,Orrie M. ; George,Harvey ; Monaco,Anthony P. ; Schwartz,Robert ; Starkovsky,Nicolas A.

Report Date : 30 MAY 1970

Pagination or Media Count : 31

Abstract : The investigation involved the preparation of chemicals suitable for immunological screening and the immunological evaluation of these compounds. Thirteen cyclophosphamide analogs were synthesized. Following a preliminary determination of their acute toxicity, these compounds were evaluated first in sheep erythrocyte (SRBC) tolerance tests, and then in skin allograft tolerance tests. Two compounds, namely phosphoramidic mustard (NSC-69,945) and cytoxyl alcohol (NSC-52,695) were found to be especially active in inducing specific tolerance in mice in the SRBC test. Of these two compounds only one, namely cytoxyl alcohol, showed also a significant activity for the prolongation of the life of skin allografts in mice. The interesting phenomenon of the breakdown of immunological tolerance by a single injection of a suitable compound was discovered during these studies. This phenomenon, which might have important implications for cancer and viral chemotherapy, has been brought about by a mixture of phosphoramidic mustard and cytoxylamine and, to a lesser extent, by compounds NSC-72,505 and NSC-72,509. (Author)

Descriptors :   (*IMMUNOLOGY, TOLERANCES(PHYSIOLOGY)), (*DRUGS, IMMUNOLOGY), TOXICITY, ERYTHROCYTES, TRANSPLANTATION, ANTIGEN ANTIBODY REACTIONS, HETEROCYCLIC COMPOUNDS, ORGANIC PHOSPHORUS COMPOUNDS, AMIDES, CANCER, VIRUS DISEASES, CHEMOTHERAPY

Subject Categories : Medicine and Medical Research
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE