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The in-vitro effects of hydroxyurea 5-FU and 5-FUdR have been extensively studied in experimental systems employing cell-line techniques. In this study we investigated the effects of these drugs on the levels of incorporation of labeled nucleosides into DNA in explants of intact rat colonic mucosa maintained in organ culture. The effects of the nucleoside transport inhibitors nitrobenzylthioinosine (NBMPR) and dipyridamole--which are modulators of antimetabolite cytotoxicity--on the incorporation of tritiated thymidine ([3H]TdR) into DNA were also studied. The incorporation of tritiated TdR into DNA was reduced by hydroxyurea but was not altered by either 5-FU or 5-FUdR. The levels of tritiated deoxyuridine were reduced by 5-FU and 5-FUdR in separate experiments; this is in keeping with thymidylate synthase inhibition. NBMPR and dipyridamole also reduced 3H-TdR incorporation into DNA. These results can be explained in terms of the known mechanisms of action of these drugs. This experimental model is therefore useful in assessing the effects of antimetabolites and nucleoside transport inhibitors in intact colonic mucosa.

Original publication

DOI

10.1007/BF02630990

Type

Journal article

Journal

In Vitro Cell Dev Biol

Publication Date

11/1991

Volume

27A

Pages

873 - 877

Keywords

Animals, Biological Transport, Colon, DNA, Dipyridamole, Hydroxyurea, Intestinal Mucosa, Male, Models, Biological, Nucleosides, Organ Culture Techniques, Pyrimidines, Rats, Rats, Inbred Strains, Thioinosine, Thymidine, Time Factors, Tritium, Uridine