Document Detail


Metabolism and selective effects of 1-beta-D-arabinofuranosylcytosine in L1210 and Host tissues in vivo.
MedLine Citation:
PMID:  1109791     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The selectivity of action of 1-beta-D-arabinofuranosylcytosine (ara-C) against leukemic cells was studied in vivo. Dynamic state tissue levels of ara-C and of its mono-, di-, and triphosphate (ara-CTP) were measured in L1210 leukemic cells and in C57BL x DBA/2 F1 host tissues at different times after various doses of the agent. The levels were correlated with inhibition of thymidine incorporation into DNA and with cytocidal effects as measured by loss of isotopically prelabeled DNA. ara-CTP levels, but not those of the mono- and diphosphates of ara-C, were higher in leukemic cells and in host cell renewal systems than in other host tissues. DNA synthesis was equally inhibited by similar levels of ara-CTP in ascitic L1210 cells, in leukemic infiltrates in liver, and in small intestine. However, L1210 cells accumulated higher levels of ara-CTP for longer periods than did small intestine, and correspondingly the inhibition of DNA synthesis was greater and more prolonged in leukemic cells. ara-C caused greater losses of prelabeled DNA in ascites cells and in infiltrated liver than in host small intestine. It appears that the differential net tissue level of ara-CTP and its duration are the determinants of chemotherapeutic efficacy of ara-C against L1210 leukemia. ara-C was the predominant nucleoside present in hydrolysates of ara-CTP fractions. By contrast, 1-beta-D-arabinofuranosyluracil predominated in hydrolysates of monophosphate nucleotide fractions from ascites cells, liver, small intestine, and blood. Monophosphate nucleotide was also present in ascites fluid and plasma.
Authors:
T C Chou; D J Hutchinson; F A Schmid; F S Philips
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  35     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1975 Jan 
Date Detail:
Created Date:  1975-04-16     Completed Date:  1975-04-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  225-36     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Ascitic Fluid / cytology
Cytarabine* / analogs & derivatives,  blood,  metabolism,  pharmacology
DNA, Neoplasm / biosynthesis
Idoxuridine / metabolism
Intestine, Small / metabolism*
Leukemia L1210 / metabolism*
Liver / metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Thymidine / metabolism
Tritium
Chemical
Reg. No./Substance:
0/DNA, Neoplasm; 10028-17-8/Tritium; 147-94-4/Cytarabine; 50-89-5/Thymidine; 54-42-2/Idoxuridine

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