Alterations in nucleoside monophosphate concentrations in 3LL tumours after combined treatment with tiazofurin and 5-hexyl-2'-deoxyuridine.
The IMP and GMP concentrations were compared after treatment with tiazofurin alone and in combination with 5-hexyl-2'-deoxyuridine (HUdR) in 3LL-HH adenocarcinoma in vivo. The elevation in IMP/GMP ratio, indicating guanylate depletion and increase of inosine-5'-monophosphate concentration, showed a dose dependence and was the highest at the 7th hour after treatment with tiazofurin. HUdR application alone caused only a modest change in the nucleotide concentration of LL-HH tumour. However, the rise of IMP but not the reduction of guanylate concentration induced by tiazofurin was remarkably mitigated by HUdR treatment, without affecting the antitumour potency of tiazofurin. Thus HUdR showed modifying activity on some of the tiazofurin-induced changes in nucleotide metabolism which appeared not to be associated with the antiproliferative activity of tiazofurin. It follows that reduced GMP concentration and not the elevation of IMP/GMP ratio could predict therapeutic responses to tiazofurin.
Pogany
G
G
Joint Research Organization of the Hungarian Academy of Sciences and Semmelweis Medical University, Department of Molecular Pathology, Budapest.
Raso
E
E
Peterszegi
G
G
Keresztfalvi
M
M
Lapis
K
K
Jeney
A
A
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003857:Deoxyuridine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006157:Guanosine Monophosphate / Q000032:analysis*; D007291:Inosine Monophosphate / Q000032:analysis*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D012254:Ribavirin / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000964:Antimetabolites, Antineoplastic; D007291:Inosine Monophosphate; D012254:Ribavirin; C064952:5-hexyl-2'-deoxyuridine; D006157:Guanosine Monophosphate; C033706:tiazofurin; D003857:Deoxyuridine