Histopathological and biochemical analyses of transplantable renal adenocarcinoma in rats induced by N-ethyl-N-hydroxyethylnitrosamine

Abstract

Transplantable renal adenocarcinoma can be readily induced in Wistar strain male rats by initiation with N-ethyl-N-hydroxy-ethylnitrosamine followed by promotion with beta-cyclodextrin. The transplantability rates of the tumors by s.c. inoculation in newborn rats were 33 and 50%, respectively, for tumors of the first and second passages, and 100% for both third and fourth passages. The transplantability rates were affected by route of inoculation; rates of 50 and 100% were observed for s.c. and i.p. inoculations, respectively. The growth rate of tumors induced by i.p. inoculation was 3-fold higher than that induced by s.c. injection. Macroscopically, most of the tumors grew in the s.c. tissue of inoculation sites. However, invasive growth of tumors in spleen, liver, stomach, peritoneum, and intestine were seen in 50% of the animals inoculated i.p.; metastatic cancers to lung were seen in 16%. Histologically, the tumors were well-differentiated adenocarcinomas composed of uniform cells resembling kidney tubular cells and appeared to be derived from normal kidney tissues. A 5-fold decrease in gamma-glutamyl transferase activity in tumor tissues was found as compared with that of nontumorous kidney tissues. Electrophoretic analysis of cellular proteins in polyacrylamide gels revealed that tumor tissues exhibited five new polypeptides with molecular weights of 81,000, 64,000, 59,000, 50,000, and 36,000 which were either lacking or undetectable in the nontumourous area and control kidney. In addition, protein banding patterns of transplantable renal tumor appeared to be more heterogeneous than those of primary kidney tumor.