| Autor: |
Spremulli EN, Crabtree GW, Dexter DL, Chu SH, Farineau DM, Ghoda LY, McGowan DL, Diamond I, Parks RE Jr, Calabresi P |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemical pharmacology [Biochem Pharmacol] 1982 Jul 15; Vol. 31 (14), pp. 2415-21. |
| DOI: |
10.1016/0006-2952(82)90538-x |
| Abstrakt: |
The toxicology and metabolism of 8-azaadenosine (8-azaAdo) were examined both as a single agent and in combination with the adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF). The LD10 (mice) for 8-azaAdo alone on a once daily for 5 days (q.d. x 5) schedule was 30 mg . kg-1 . day-1. When the animals were pretreated with 0.1 mg . kg-1 . day-1 of dCF, the LD10 dose was reduced to 10 mg . kg-1 . day-1 x 5. The major organ toxicity seen was hepatic. Bone marrow cellularity was only slightly altered at the LD10 dose. 8-AzaAdo nucleotides were detected in the livers of treated mice as determined by high performance liquid chromatography. Further, after 2 hr of incubation, isolated rat hepatocytes accumulated 8-azaATP to levels of 2.2 mumoles/g of cells with 8-azaAdo (1 mM) alone and to 4.3 mumoles/g of cells when 8-azaAdo was used in combination with dCF (1 microgram/ml). ATP levels decreased to below the limits of detection after 2 hr in cells treated with the combination. The replacement of cellular ATP by 8-azaATP may provide an explanation for the hepatotoxicity observed in the murine toxicology studies. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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