CHARACTERIZATION OF CANINE MDR1 MESSENGER-RNA - ITS ABUNDANCE IN DRUG-RESISTANT CELL-LINES AND IN-VIVO

Background: Overexpression of the MDR1 gene often contributes to antin eoplastic drug resistance. The purpose of this study was to characteri ze the canine MDR1 mRNA homologue and evaluate its expression in both canine cell lines and lymphomas. Materials and Methods: The abundance of the canine MDR1 transcript was assessed in three resistant cell lin es and in pretreatment canine lymphoma wing semi-quantitative RT/PCR. Results: Canine transcript was 4.5 Kb with 9.3% sequence homology to h uman MDR1, and 90% homology to mouse and hamster equivalent genes. Inc rease in MDR1 transcript levels was observed in three progressively re sistant canine cell lines. De novo MDR1 transcript expression was inde pendent of response to therapy in dogs with lymphoma. Conclusions: We conclude that the canine MDR1 mRNA homologue is structurally similar t o the human transcript. Expression of MDR1 mRNA correlates with in vit ro drug sensitivity but does not correlate with in vivo doxorubicin se nsitivity in canine lymphoma.