Differences in deoxycytidine metabolism in mouse and rat

Area of Science:

• Biochemistry
• Pharmacology
• Comparative Physiology

Background:

• Bone marrow macrophages in rats and mice release deoxycytidine from phagocytosed nuclei.
• Significant concentration differences of deoxycytidine exist in rat (18 microM) versus mouse (<0.1 microM) plasma.

Purpose of the Study:

• To investigate the metabolic basis for differential deoxycytidine levels in rat and mouse plasma.
• To explore how these metabolic differences influence sensitivity to nucleoside compounds.

Main Methods:

• Enzyme assays were performed on tissue extracts to quantify deoxycytidine kinase and deaminase activities.
• Cytotoxicity assays assessed the effects of deoxyadenosine on mouse lymphoid cells cultured in rat serum.

Main Results:

• Both rat and mouse spleen exhibit high deoxycytidine kinase activity.
• Mouse organs possess significant deoxycytidine deaminase activity, while rat tissues show virtually none.
• This lack of deaminase in rats explains elevated plasma deoxycytidine levels.

Conclusions:

• A key metabolic difference lies in deoxycytidine deaminase activity between rats and mice.
• This metabolic disparity likely accounts for observed discrepancies in pharmacological responses to nucleoside analogs in these species.