Abstract
Administration of N-(phosphonacetyl)-L-aspartic acid (PALA) is ineffective in treating mice bearing the parent P388 leukemia line; however, such treatment becomes highly effective when a cell line, P388/ACIA, derived from P388/0 was selected for resistance to another antimetabolite, acivicin. The observed phenomenon of collateral sensitivity is associated with a significantly higher inhibition of the specific activity of carbamyl phosphate synthetase II, pyrimidine nucleoside kinases, adenine phosphoribosyl transferase, and hypoxanthine phosphoribosyl transferase in the PALA-sensitive line, P388/ACIA. Twenty-four hr following administration of PALA, 200 mg/kg, the 10% lethal dose i.p. to tumor-bearing mice, the intracellular concentrations of uridine triphosphate and cytidine triphosphate were decreased in the P388/ACIA, PALA-sensitive cells, whereas no significant change in the corresponding nucleotide pool sizes was observed in P388/0, PALA-resistant line. Moreover, the purine nucleotide pool demonstrated a significant expansion of adenosine triphosphate and a guanosine triphosphate only in the P388/ACIA line following a similar treatment with PALA. It is proposed that the imbalance in the generation of pyrimidine and purine nucleoside triphosphate pools may explain the observed collateral sensitivity to PALA in P388/ACIA leukemia line.
| Original language | English |
|---|---|
| Pages (from-to) | 1598-1601 |
| Number of pages | 4 |
| Journal | Cancer Research |
| Volume | 43 |
| Issue number | 4 |
| State | Published - Jan 1 1983 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Collateral sensitivity to N-(phosphonacetyl)-L-aspartic acid in a line of P388 leukemia cells selected for resistance to L-(αS,5S)-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin). / Ardalan, Bach; Jayaram, H. N.; Johnson, R. K.
In: Cancer Research, Vol. 43, No. 4, 01.01.1983, p. 1598-1601.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Collateral sensitivity to N-(phosphonacetyl)-L-aspartic acid in a line of P388 leukemia cells selected for resistance to L-(αS,5S)-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin)
AU - Ardalan, Bach
AU - Jayaram, H. N.
AU - Johnson, R. K.
PY - 1983/1/1
Y1 - 1983/1/1
N2 - Administration of N-(phosphonacetyl)-L-aspartic acid (PALA) is ineffective in treating mice bearing the parent P388 leukemia line; however, such treatment becomes highly effective when a cell line, P388/ACIA, derived from P388/0 was selected for resistance to another antimetabolite, acivicin. The observed phenomenon of collateral sensitivity is associated with a significantly higher inhibition of the specific activity of carbamyl phosphate synthetase II, pyrimidine nucleoside kinases, adenine phosphoribosyl transferase, and hypoxanthine phosphoribosyl transferase in the PALA-sensitive line, P388/ACIA. Twenty-four hr following administration of PALA, 200 mg/kg, the 10% lethal dose i.p. to tumor-bearing mice, the intracellular concentrations of uridine triphosphate and cytidine triphosphate were decreased in the P388/ACIA, PALA-sensitive cells, whereas no significant change in the corresponding nucleotide pool sizes was observed in P388/0, PALA-resistant line. Moreover, the purine nucleotide pool demonstrated a significant expansion of adenosine triphosphate and a guanosine triphosphate only in the P388/ACIA line following a similar treatment with PALA. It is proposed that the imbalance in the generation of pyrimidine and purine nucleoside triphosphate pools may explain the observed collateral sensitivity to PALA in P388/ACIA leukemia line.
AB - Administration of N-(phosphonacetyl)-L-aspartic acid (PALA) is ineffective in treating mice bearing the parent P388 leukemia line; however, such treatment becomes highly effective when a cell line, P388/ACIA, derived from P388/0 was selected for resistance to another antimetabolite, acivicin. The observed phenomenon of collateral sensitivity is associated with a significantly higher inhibition of the specific activity of carbamyl phosphate synthetase II, pyrimidine nucleoside kinases, adenine phosphoribosyl transferase, and hypoxanthine phosphoribosyl transferase in the PALA-sensitive line, P388/ACIA. Twenty-four hr following administration of PALA, 200 mg/kg, the 10% lethal dose i.p. to tumor-bearing mice, the intracellular concentrations of uridine triphosphate and cytidine triphosphate were decreased in the P388/ACIA, PALA-sensitive cells, whereas no significant change in the corresponding nucleotide pool sizes was observed in P388/0, PALA-resistant line. Moreover, the purine nucleotide pool demonstrated a significant expansion of adenosine triphosphate and a guanosine triphosphate only in the P388/ACIA line following a similar treatment with PALA. It is proposed that the imbalance in the generation of pyrimidine and purine nucleoside triphosphate pools may explain the observed collateral sensitivity to PALA in P388/ACIA leukemia line.
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UR - http://www.scopus.com/inward/citedby.url?scp=0020538535&partnerID=8YFLogxK
M3 - Article
C2 - 6831405
AN - SCOPUS:0020538535
VL - 43
SP - 1598
EP - 1601
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 4
ER -