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Metabolism of Deoxycytidine, Thymine, and Deoxythymidine in the Hamster¹

Department of Microbiology, University of Mississippi Medical Center, Jackson, Mississippi 39216

The ability of growing and of mature Syrian hamsters to anabolize (to liver DNA) or catabolize (to ¹⁴CO₂) graded amounts of [2-¹⁴C]deoxythymidine (TdR), thymine, or deoxycytidine (CdR) was measured in vivo. Of the three precursors, CdR labeled DNA most efficiently and, as expected, incorporation of all three into DNA was greater in younger animals. The catabolism of [2-¹⁴C]CdR to respired ¹⁴CO₂ was dose dependent and showed no sings whatsoever of saturation, even with the highest dose (> 20 µmoles/g liver). In contrast, TdR and thymine were catabolized more slowly and saturation was approached with modest doses. The excretion of CdR in the urine was low and independent of dose, while excretion of TdR and thymine was greater and was dose dependent. Rats tested with an intermediate dose of CdR did not catabolize significant quantities to ¹⁴CO₂, but did excrete considerably more [¹⁴C]CdR into the urine than did hamsters. These and other findings suggest that, while the rat and the hamster metabolize thymine (and TdR as well) in a similar fashion, they metabolize CdR quite differently, probably because the hamster has a much higher level of nucleoside aminohydrolase which deaminates CdR and related compounds. Because the human also has a very high level of this enzyme, the hamster appears to be a superior animal model for the study of cytosine-containing compounds intended for human use.

¹ This investigation was supported in part by American Cancer Society Grants T-357 and PRA-40, and by NIH Grants AI-69, 5-K3-7021, and 5-SO1-RR05386. A preliminary report on some phases of this work has been presented (20).

² Present address: Department of Cell and Molecular Biology, Medical College of Georgia, Augusta, Ga.

³ Present address: Department of Surgery, University of Kansas Medical Center, Kansas City, Kans.

Received 8/27/74. Accepted 2/11/75.

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