Strain variation in renal carcinogenesis by N-ethyl-N-hydroxyethylnitrosamine in F1 (Wistar-Fischer) rats

The present study was conducted to compare the incidences of renal tumors in Wistar (W), Fischer (F) and F1 rats (WF: female Wistar rats x male Fischer rats; FW: female Fischer rats x male Wistar rats) induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN). Levels of 8-OHdG in renal DNA were also investigated in Wistar and Fischer rats. After 2000 ppm of EHEN was administered orally for 2 weeks, the animals were fed basal diet until week 32. Wistar males and females demonstrated significantly higher sensitivity regarding induction of renal lesions, while both WF and FW rats had similar incidences, generally intermediate between those for the two parent strains. The formation of 8-OHdG was maximal 60-180 min after an intraperitoneal dose of 750 mg/kg to Wistar and Fischer rats, which correlates with the increase tending to the incidence of renal tumors in male and female Wistar and Fischer rats. The results suggest that EHEN induction of renal tumors is related to oxygen radical damage and that the genes in the Wistar strain responsible for the sensitivity are not inherited in a sex-dependent fashion, despite the male being more susceptible.