Utilization of 3H from deoxyuridine and thymidine for synthesis of DNA and other macromolecules in various organs of the rat

Hopkins, Harold A.; Wakefield, Jean A.

doi:10.1016/0006-2952(77)90130-7

Cited by 15 publications

(8 citation statements)

References 23 publications

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“…This is not the case since side experiments showed that HeLa M-1 cells in culture discriminate in favour of [14C]TdR over [jHJdUdR for incorporation into DNA by a factor of 12 to 1 (data not shown). This is consistent with work in the rat demonstrating ratios of incorporation into DNA of [3H]TdR to [jHIdUdR by 7.03 in the intestine (the ratio was 14.9, 6.4 and 3.4 in the thymus, spleen and marrow respectively) (Hopkins & Wakefield, 1977). These results also indicate that there would be relatively little incorporation of dUdR which had been produced by deiodination of [3H]IdUdR on entry into the cell.…”

Section: Discussionsupporting

confidence: 90%

Local Re‐Utilization of Thymidine In Normal Mouse Tissues As Measured With Iododeoxyuridine

Quackenbush

Shields

1988

Cell Proliferation

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Abstract. Thymidine (TdR) and its analogue, iododeoxyuridine (IdUdr), were used to quantitate nucleoside re‐utilisation in vivo. Significantly different results are obtained, however, depending upon what form of isotopically labelled iododeoxyuridine is used. No measurable local thymidine re‐utilization was found in mouse thymus, spleen or bone marrow when the retention of [3H]IdUdR was compared with [14C]TdR. On the other hand, significant differences were found between the retention of [125I]IdUdR and [3H]IdUdR, which is attributed to de‐iodination of iododeoxyuridine. Some thymidine re‐utilization was found in duodenum using both [3H]IdUdR and [125I]IdUdR. Information on the in vivo distribution of TdR and the contention that a large degree of TdR re‐utilization in the thymus is evidence of extensive cell death must be re‐interpreted in the light of these results. In addition, evidence for little or no local re‐utilization in some tissues will greatly simplify the use of [11C]TdR as an imaging agent for measuring tissue proliferation in vivo with positron emission tomography (PET).

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Section: Discussionsupporting

confidence: 90%

Local Re‐Utilization of Thymidine In Normal Mouse Tissues As Measured With Iododeoxyuridine

Quackenbush

Shields

1988

Cell Proliferation

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“…Membrane transport mechanisms may also be relevant to the uptake of the labelled nucleoside and endogenous nucleoside and nucleotide concentrations may cause dilutional effects. Little is known about the effect of the kinases on nucleoside uptake although thymidine phosphorylation is not rate limiting for thymidine uptake (Hopkins & Wakefield, 1977). Indeed no correlation has been found between thymidine uptake and thymidine kinase activity in normal bone marrow and in various haematological disorders (Wickramasinghe et al, 1975) and also preliminary data in our laboratory suggest that the differences in nucleoside incorporation cannot be explained by differences in TdR and CdR kinase activities (Sylwestrowicz et a!, in preparation).…”

Section: Discussionmentioning

confidence: 92%

DNA Synthesis in Thymic‐Acute Lymphoblastic Leukaemia

et al. 1981

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Summary. Deoxyribonucleoside triphosphate (dNTP) concentrations were measured in bone marrow and peripheral blood leucocytes from seven patients with acute Thy‐lymphoblastic leukaemia (Thy‐ALL), 12 patients with acute myeloblastic leukaemia and 15 patients with acute non‐T, non‐B lymphoblastic leukaemia (c‐ALL), and in thymocytes from patients with myasthenia gravis. Labelled thymidine and deoxycytidine incorporation into DNA was also studied. In Thy‐ALL, dNTP concentrations were markedly increased compared with those in the other acute leukaemias. The dNTP concentrations in thymocytes were, however, similar to those in Thy‐ALL. 3H‐nucleoside incorporation studies showed a marked difference in labelled deoxycytidine incorporation and particularly in the deoxycytidine/thymidine DNA labelling ratio between Thy‐ALL and the other cell types. We conclude that the pathways of DNA synthesis in Thy‐ALL blasts are different from those in the cells from other acute leukaemias and some but not all these differences may correspond to differences between normal cortical thymocytes and bone marrow cells.

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“…Interpretations regarding DNA synthesis based solely on measurements of acid-insoluble radioactivity might be complicated by radioactivity associated with cellular macromolecules other than DNA (Goldspink & Goldberg, 1973;Hopkins & Wakefield, 1977;Maurer, 1981). However, as indicated from the present study, this does not seem to be a great problem when using 16-jHITdR.…”

Section: Discussionmentioning

confidence: 99%

“…Depending on the cell type, TdR nucleotides are either incorporated into DNA or after entering the intracellular precursor pool are rapidly degraded or persist for a longer period (Taheri, Wickremasinghe & Hoffbrand, 198 1). It is well known that only a minor fraction of the exogenously administered TdR will be used for incorporation into DNA (Hopkins & Wakefield, 1977;Tew & Taylor, 1978). The main degradation products of TdR are known to be P-aminoisobutyric acid and P-ureidoisobutyric acid, which are further metabolized to CO,, NH,, and water (Tew & Taylor, 1978;Bols et al, 1980).…”

Section: B Hellman and S Ullbergmentioning

confidence: 99%

Rate of Incorporation of R3hlthymidine In Various Tissues of the Mouse A basis for the evaluation of genotoxic effects of chemicals

Hellman

Ullberg

1986

Cell Proliferation

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13HlThymidine has been extensively used as a selective pr6cursor to DNA in studies on the kinetics of cell proliferation. We have become interested in measuring early inhibition of the DNA synthesis in various organs of intact animals for detecting genotoxic properties of chemicals. Such experiments should, for convenience and to achieve a large capacity, be performed in the simplest way possible.The present paper deals with some practical aspects on the use of I3H]thymidine in uivo. C6-3HlThymidine was injected intraperitoneally in mice and the uptake of

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Utilization of 3H from deoxyuridine and thymidine for synthesis of DNA and other macromolecules in various organs of the rat

Cited by 15 publications

References 23 publications

Local Re‐Utilization of Thymidine In Normal Mouse Tissues As Measured With Iododeoxyuridine

Local Re‐Utilization of Thymidine In Normal Mouse Tissues As Measured With Iododeoxyuridine

DNA Synthesis in Thymic‐Acute Lymphoblastic Leukaemia

Rate of Incorporation of R3hlthymidine In Various Tissues of the Mouse A basis for the evaluation of genotoxic effects of chemicals

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