STRAIN DIFFERENCES IN SENSITIVITY TO THE PROMOTING EFFECT OF SODIUM L-ASCORBATE IN A 2-STAGE RAT URINARY-BLADDER CARCINOGENESIS MODEL

Rat strain differences in sensitivity to the promoting effect of sodiu m L-ascorbate (SA) on the development of urinary bladder tumors were i nvestigated. In experiment 1, WS/Shi (WS), ODS/Shi-od/od (ODS), and LE W/Crj (LEW) rats were initiated with 0.05% N-butyl-N-(4-hydroxybutyl)- nitrosamine (BBN) in their drinking water and subsequently given basal Oriental MF diet (M) with or without a 5% SA supplement. In LEW rats the SA treatment increased the induction of neoplastic lesions in the urinary bladder, whereas WS and ODS animals proved unresponsive to its promoting effects. In experiment 2, WS and F344 rats were maintained on two kinds of commercial basal diets, M and CLEA CA-1 (C), during ad ministration of SA, since dietary factors can influence promoting effe cts. Feeding M during the promotion period in F344 rats yielded signif icantly more neoplastic lesions than feeding C, but in WS rats no such dietary influence was apparent. In experiment 3, strain differences i n biosynthesis of alpha-2u-globulin (alpha(2u)-g) were assessed becaus e both alpha(2u)-g in the urine and administration of sodium salts of organic acids such as SA have been reported to be involved in tumor pr omotion. Immunohistochemical analysis of renal tubules and Western blo tting analysis of urine revealed the presence of alpha(2u)-g in all th ree strains examined. These data suggest that differences in susceptib ility to promotion are due to genetic factors rather than dietary fact ors and the ability to synthesize alpha(2u)-g.