Abstract |
Treatment with a combination (PMA) of (N-phosphonacetyl)- L-aspartic acid ( PALA), methylmercaptopurine riboside (MMPR), and 6-aminonicotinamide (6AN) induced partial regressions of CD8F1 murine mammary tumors and provided for tumor growth inhibition without regression of Colon 38 tumors. HPLC- nucleotide pool analysis of CD8 mammary tumors obtained at various times after treatment with PMA revealed that MMPR-5'-phosphate, which inhibits de novo purine nucleotide biosynthesis, was constant at levels of approximately 2.5 nmol/mg protein for 72 hr after treatment. In contrast, the MMPR-5'-phosphate levels of C38 tumors decreased from 24-hr levels at 1.5 nmol/mg protein with a half-time of about 24 hr. Treatment of CD8 tumor-bearing mice with iodotubercidin, a potent inhibitor of adenosine/MMPR kinase, at various times after PMA, reversed both the accumulation of high levels of MMPR-5'-phosphate and the number of partial tumor regressions. These data demonstrate that a cycle of MMPR rephosphorylation is active in the CD8 mammary tumor and suggest that this recycling of MMPR is important for the optimal effect of PMA treatment.
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Authors | L D Nord, R L Stolfi, J R Colofiore, D S Martin |
Journal | Biochemical pharmacology
(Biochem Pharmacol)
Vol. 51
Issue 5
Pg. 621-7
(Mar 08 1996)
ISSN: 0006-2952 [Print] England |
PMID | 8615898
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Aspartic Acid
- 6-Aminonicotinamide
- Methylthioinosine
- sparfosic acid
- Adenosine Triphosphate
- Adenosine Kinase
- Phosphonoacetic Acid
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Topics |
- 6-Aminonicotinamide
(administration & dosage)
- Adenosine Kinase
(antagonists & inhibitors)
- Adenosine Triphosphate
(metabolism)
- Animals
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Aspartic Acid
(administration & dosage, analogs & derivatives)
- Mammary Neoplasms, Experimental
(drug therapy, metabolism)
- Methylthioinosine
(administration & dosage, metabolism)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred DBA
- Phosphonoacetic Acid
(administration & dosage, analogs & derivatives)
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