Tumor Response and Apoptosis of N1-S1 Rodent Hepatomas in Response to Intra-arterial and Intravenous Benzamide Riboside

Abstract

Benzamide riboside (BR) induces tumor apoptosis in multiple cell lines and animals. This pilot study compares apoptosis and tumor response in rat hepatomas treated with hepatic arterial BR (IA) or intravenous (IV) BR. A total of 10(6) N1-S1 cells were placed in the left hepatic lobes of 15 Sprague-Dawley rats. After 2 weeks, BR (20 mg/kg) was infused IA (n=5) or IV (n=5). One animal in each group was excluded for technical factors, which prevented a full dose administration (1 IA and 1 IV). Five rats received saline (3 IA and 2 IV). Animals were killed after 3 weeks. Tumor volumes after IA and IV treatments were analyzed by Wilcoxon rank sum test. The percentage of tumor and normal liver apoptosis was counted by using 10 fields of TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-stained slides at 40× magnification. The percentage of apoptosis was compared between IV and IA administrations and with saline sham-treated rats by the Wilcoxon rank sum test. Tumors were smaller after IA treatment, but this did not reach statistical significance (0.14 IA vs. 0.57 IV; P=0.138). There was much variability in percentage of apoptosis and no significant difference between IA and IV BR (44.49 vs. 1.52%; P=0.18); IA BR and saline (44.49 vs. 33.83%; P=0.66); or IV BR and saline (1.52 vs. 193%; P=0.18). Although differences in tumor volumes did not reach statistical significance, there was a trend toward smaller tumors after IA BR than IV BR in this small pilot study. Comparisons of these treatment methods will require a larger sample size and repeat experimentation.