Title

Is Doxorubicin Cardiotoxicity Protection by Reduced Expression of the Cbr1 Gene Observed in Backgrounds Other Than 129 SVE?

Publication Year

2005

Keywords

Doxorubicin, toxicity, human carbonyl reductase enzyme, Cbr1

Disciplines

Biology | Life Sciences

Abstract

Doxorubicin (DOX) is an effective chemotherapy drug which is restricted in use by its chronic and progressive cardiotoxic effects. A major metabolite of DOX, doxorubicinol (DOXol), has been suggested as a possible contributor to the DOX-induced cardiotoxicity. The human carbonyl reductase enzyme (CBR1) is known to metabolize DOX into DOXol. A Previous study has shown that DOX-induced cardiotoxicity protection can be attained by reducing the carbonyl reductase expression in the heart. This observation was taken from a study of 129 SVE background mice with a knockout Cbr1 allele. In the present study, mice of three other different genetic backgrounds, as well as 129 SVE, were used to validate the results from the previous study as well as to determine if the DOX-induced toxivity is significantly different between strains. The mice were injected with 20 mg/kg DOX , and then weight and survival were assessed. The results were analyzed by Kaplan-Meir and Cox Regression tests using the NCSS graphic and statistical software program. Results determined that a reduction in Cbr1 expression in mice did not cause significant proteciton against DOX-induced toxicity, and genetic background was not an influence. In fact, the previous finding in 129 SVE mice was not replicated. It was observed that interactions between initial weight, dose, and gender significantly influenced survival.

Department 1 Awarding Honors Status

Biology

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