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Differences in deoxycytidine metabolism in mouse and rat
Abstract:
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.
Insights
Differences in deoxycytidine metabolism between rats and mice explain varying responses to nucleoside drugs. Rats have high plasma deoxycytidine due to low deaminase activity, unlike mice.
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.