Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P00492 (
hypoxanthine-guanine phosphoribosyltransferase
)
2,385
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Decomposition of the antitumor agent 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (
DTIC
,
Dacarbazine
) produces several potentially toxic compounds, the concentration of which depend on incubation parameters such as pH, temperature and illumination. The action of
DTIC
on chinese hamster ovary (CHO) cell clone formation in the dark (7-8-day incubation) reflects the slow formation of 2-azahypoxanthine.
Hypoxanthine-guanine phosphoribosyltransferase
(HGPRT, EC 2.4.2.8)-deficient cells are resistant to
DTIC
under these conditions, reflecting their inability to utilize 2-azahypoxanthine. The toxicity of
DTIC
in conventional survival experiments (1-2-h exposure to drug) is dependent upon illumination and is highly influenced by the pH of the medium. Toxicity of
DTIC
in these experiments appears to reflect rapid accumulation of the immediate photodecomposition product of the drug, 4-diazoimidazole-5-carboxamide (DZC), since HGPRT-deficient cells are not resistant to
DTIC
under these conditions. The biologically initiated pathway of
DTIC
action (enzymatic hydroxylation) has little, if any, role in the action of this agent toward cultured CHO cells.
...
PMID:Mechanisms of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (Dacarbazine) cytotoxicity toward Chinese hamster ovary cells in vitro are dictated by incubation conditions. 374 46
