Quantitative analysis of mRNA for 10 different drug resistance factors in dogs with lymphoma.

Expression levels of ABCB1, ABCC1, Lung resistance-associated protein (LRP), ABCG2, p53, p21(waf1), Bcl-2, CD40L, glutathione S-transferase alpha (GSTα), and O⁶-methylguanine-DNA-methyltransferase (MGMT) genes, and mutation of p53 gene were examined in 23 dogs with multicentric high-grade lymphoma to explore their association with drug resistance of the tumor cells. Dogs were divided into chemotherapy-sensitive (n=13) and -resistant (n=10) groups according to the response to a 6-month modified version of the University of Wisconsin (UW)-Madison chemotherapy protocol (UW-25), and expression levels of these factors and frequency of p53 gene mutation were compared between groups. No significant differences were observed in expression levels of each factor between groups. However, 4 dogs in the chemotherapy-resistant group showed high expression of ABCB1. No significant difference was observed in the frequency of p53 mutation between groups. A possible association of ABCB1 with resistance to UW-25 was shown, but no uniform mechanism associated with drug resistance could be identified in dogs with lymphoma.