Differential deoxyadenosine toxicity to immature rabbit cartilage in vitro. A model for the chondro-osseous dysplasia of adenosine deaminase deficiency.
Deoxyadenosine metabolism was investigated in rabbit growth plate and articular cartilage to elucidate the biochemical basis for the chondro-osseous dysplasia observed in adenosine deaminase (ADA) deficiency. Models of ADA deficiency, the combination of deoxy-adenosine and either of 2 ADA inhibitors, were selectively toxic to immature cartilage, supporting the hypothesis that the chondro-osseous dysplasia of ADA deficiency is the consequence of the enzyme deficiency. Depletion of ATP may play a role in the altered chondrocyte viability and function observed in this model.
Wortmann
R L
RL
Department of Internal Medicine, Clement J. Zablocki Veterans Administration Medical Center, Milwaukee, WI 53295.
Veum
J A
JA
Ryan
L M
LM
Cheung
H S
HS
D000243:Adenosine Deaminase / Q000172:deficiency*; D058892:Adenosine Deaminase Inhibitors; D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001842:Bone and Bones / Q000473:pathology; D002356:Cartilage / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D003839:Deoxyadenosines / Q000378:metabolism / Q000633:toxicity*; D004195:Disease Models, Animal; D009700:Nucleoside Deaminases / Q000172:deficiency*; D011687:Purines / Q000378:metabolism; D011817:Rabbits
D058892:Adenosine Deaminase Inhibitors; D003839:Deoxyadenosines; D011687:Purines; D000255:Adenosine Triphosphate; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase