skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: INHIBITION OF THE REJECTION OF RENAL HOMOGRAFTS IN DOGS BY DRUGS

Abstract

The use of cytostntic drugs and whole-body irradiation to reduce the immunologic response to kidney transplantation is reported. In the absence of such trentments, canine renal transplarts usually cease to function 5 to 8 days after operation, although occasionally a transplant will function for 14 days. To prevent rejection of homologous tissue, a very high dose of x rays is necessary. To inhibit renal homograft rejection experimentally, it is necessary to destroy the hematopoietic tissue in the bone marrow. Thus, below 1000-r doses of total-body x irradiation, typical rejection occurs, while above 1300 r rejection is inhibited, but only one of the dogs studied survived more than a few days. The use of thiopurines and other drugs was compared with sublethal whole- body irradiation for effectiveness in prolonging homologous kidney grafts in dogs. The percentages of dogs (104 were studied) surviving beyond 3 months after bilateral renal homografts and treated with x rays, 6-mercaptopurine, nitrogen mustard, cyclophosphamide, Actinomycin D, Actinomycin C were 8, 0, 17, 0, 20, and 25%, respectively. The respective mean survival times with these treatments were 34, 22, 32, 16, 28, and 58 days. When the 104 animals from all groups are considered, only 10% survived beyondmore » 3 months. This marked variability could be attributed to one or a combination of the following: variability of the aggressiveness of immune reaction in different animals; alternative pathways of purine metabolism that can bypass the specific blocks of the purine analogs; variability in absorption and excretion of the drugs; chance relation of histocompatibility factors between random outbred dogs. The significance of these results for human kidney grafting is discussed. Of the various methods of preventing renal homograft rejection discussed, thiopurine drugs appear to be the only agents that have a repeatable effect on adult animals and the lethal effect of irradiation above 1300 r precludes the use of such a dose clinically. (BBB)« less

Authors:
Publication Date:
Research Org.:
Westminster Medical School, London
OSTI Identifier:
4058461
NSA Number:
NSA-18-017495
Resource Type:
Journal Article
Journal Name:
Ann. Roy. Coll. Surg. Engl.
Additional Journal Information:
Journal Volume: Vol: 32; Other Information: Orig. Receipt Date: 31-DEC-64
Country of Publication:
Country unknown/Code not available
Language:
English
Subject:
BIOLOGY AND MEDICINE; ACTINOMYCIN; AMIDES; ANTIBIOTICS; ANTIMITOTIC DRUGS; BIOCHEMISTRY; BLOOD FORMATION; BODY; BONE MARROW; CYTOLOGY; DIFFUSION; DISTRIBUTION; DOGS; DRUGS; EFFICIENCY; HETEROCYCLICS; IMMUNITY; IRRADIATION; KIDNEYS; LETHAL DOSE; MEDICINE; METABOLISM; NITROGEN MUSTARD; NUMERICALS; ORGANIC NITROGEN COMPOUNDS; ORGANIC SULFUR COMPOUNDS; PHOSPHORIC ACID; PHYSIOLOGY; PURINES; QUANTITY RATIO; RADIATION DOSES; RADIATION INJURIES; SAFETY; SENSITIVITY; STATISTICS; SURGERY; SURVIVAL TIME; TISSUES; TOXICITY; TRANSPLANTS; VARIATIONS; X RADIATION

Citation Formats

Calne, R Y. INHIBITION OF THE REJECTION OF RENAL HOMOGRAFTS IN DOGS BY DRUGS. Country unknown/Code not available: N. p., 1963. Web.
Calne, R Y. INHIBITION OF THE REJECTION OF RENAL HOMOGRAFTS IN DOGS BY DRUGS. Country unknown/Code not available.
Calne, R Y. 1963. "INHIBITION OF THE REJECTION OF RENAL HOMOGRAFTS IN DOGS BY DRUGS". Country unknown/Code not available.
@article{osti_4058461,
title = {INHIBITION OF THE REJECTION OF RENAL HOMOGRAFTS IN DOGS BY DRUGS},
author = {Calne, R Y},
abstractNote = {The use of cytostntic drugs and whole-body irradiation to reduce the immunologic response to kidney transplantation is reported. In the absence of such trentments, canine renal transplarts usually cease to function 5 to 8 days after operation, although occasionally a transplant will function for 14 days. To prevent rejection of homologous tissue, a very high dose of x rays is necessary. To inhibit renal homograft rejection experimentally, it is necessary to destroy the hematopoietic tissue in the bone marrow. Thus, below 1000-r doses of total-body x irradiation, typical rejection occurs, while above 1300 r rejection is inhibited, but only one of the dogs studied survived more than a few days. The use of thiopurines and other drugs was compared with sublethal whole- body irradiation for effectiveness in prolonging homologous kidney grafts in dogs. The percentages of dogs (104 were studied) surviving beyond 3 months after bilateral renal homografts and treated with x rays, 6-mercaptopurine, nitrogen mustard, cyclophosphamide, Actinomycin D, Actinomycin C were 8, 0, 17, 0, 20, and 25%, respectively. The respective mean survival times with these treatments were 34, 22, 32, 16, 28, and 58 days. When the 104 animals from all groups are considered, only 10% survived beyond 3 months. This marked variability could be attributed to one or a combination of the following: variability of the aggressiveness of immune reaction in different animals; alternative pathways of purine metabolism that can bypass the specific blocks of the purine analogs; variability in absorption and excretion of the drugs; chance relation of histocompatibility factors between random outbred dogs. The significance of these results for human kidney grafting is discussed. Of the various methods of preventing renal homograft rejection discussed, thiopurine drugs appear to be the only agents that have a repeatable effect on adult animals and the lethal effect of irradiation above 1300 r precludes the use of such a dose clinically. (BBB)},
doi = {},
url = {https://www.osti.gov/biblio/4058461}, journal = {Ann. Roy. Coll. Surg. Engl.},
number = ,
volume = Vol: 32,
place = {Country unknown/Code not available},
year = {1963},
month = {5}
}