Susceptibility of Four F1 Hybrids of Male Rats to the Promoting Effects of Sodium L-ascorbate in Two-Stage Urinary Bladder Carcinogenesis

In the two-stage rat urinary bladder carcinogenesis model with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as an initiator and sodium L-ascorbate (Na-AsA) as a promoter, we previously reported that F344/DuCrj (F344) and LEW/Crj (Lewis) rats were sensitive, whereas WS/Shi (WS) and ODS/Shi-od/od (ODS) rats were resistant. In the present study, for the development of a model useful to the QTL analysis of host genes, we examined the susceptibility to Na-AsA promotion in (F344 × WS)F1, (F344 × ODS)F1, (Lewis × WS)F1, and (Lewis × ODS)F1 hybrids of male rats. Rats were given 0.05% BBN in their drinking water for 4 weeks and then a basal diet with or without a 5% Na-AsA supplement for 32 weeks. In urine of all F1 hybrids, Na-AsA elevated pH and concentrations of sodium ion and total ascorbic acid. There were not significant differences for susceptibilities to BBN alone among the four F1 hybrids. In all F1 hybrids, administration of Na-AsA increased urinary bladder carcinogenesis when compared to the matched control rats given BBN alone. Susceptibilities to Na-AsA promotion were high in (F344 × WS)F1 and (F344 × ODS)F1 hybrids, whereas they were mild in (Lewis × WS)F1 and (Lewis × ODS)F1 hybrids. The present results therefore indicate that F1 hybrids among the F344, ODS, Lewis and WS strains may be a useful model for analyzing host genes susceptible to Na-AsA promotion in rat bladder carcinogenesis.