Differences in deoxycytidine metabolism in mouse and rat.

Bone-marrow macrophages from both rat and mouse release deoxycytidine derived from phagocytosed nuclei. Mouse plasma contains no detectable deoxycytidine (less than 0.1 microM), whereas the concentration in rat plasma is 18 microM. Enzyme assays of tissue extracts show that both mouse and rat spleen contain high deoxycytidine kinase activity. Mouse organs, including kidney, liver and lung, also have deoxycytidine deaminase activity. In contrast, rat tissues have virtually no deoxycytidine deaminase activity. Lack of deaminase provides an explanation for the presence of deoxycytidine in rat plasma. Cytotoxicity assays show that cultured mouse lymphoid cells grown in undialysed rat serum are more resistant to cytotoxic effects of deoxyadenosine than are those cells grown in dialysed rat serum. The results suggest that a major difference in deoxycytidine metabolism between mouse and rat may account for discrepancies in the pharmacological response of the two animals to certain nucleoside compounds.