INHIBITING EFFECTS OF DIETHYLMALEATE OR NH_4Cl ON NaHCO_3, BUT NOT BUTYLATED HYDROXYANISOLE, PROMOTION OF URINARY BLADDER CARCINOGENESIS IN MALE F344 RATS INITIATED WITH N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE

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The modifying potential of diethylmaleate (DEM) and NH_4Cl on promotion by butylated hydroxyanisole (BHA) or NaHCO_3 of urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was investigated. Six week old animals received 0.05% BBN for 4 weeks and then BHA(2%)+DEM(0.15%), BHA+NH_4Cl(1%), NaHCO_3(3%)+DEM, NaHCO_3+NH_4Cl, BHA, DEM, NH_4Cl or no supplement, administered during experimental weeks 5-36. BHA and NaHCO_3 clearly amplify the induction of papillary or nodular (PN) hyperplasias and papillomas in rats initiated with BBN. The promoting activity of BHA was not affected by simultaneous administration of DEM or NH_4Cl. The enhancing effects of NaHCO_3, in contrast, were clearly diminished by concurrent administration of either of these agents. DEM itself did not influence lesion development whereas NH_4Cl reduced the incidence of papillomas. In a second experiment, rats exposed to the same protocol were killed at week 8, and assessed for levels of lipid peroxides in the bladder tissue. No remarkable alterations were observed in any group. Thus, the fact that DEM did exert inhibiting effects on tumor promotion by NaHCO_3 without decreasing the urinary sodium ion concentration or pH and influence on lipidperoxide levels, suggests essential differences in the mechanisms of action of different types of bladder promoters.
日本トキシコロジー学会の論文
1994-11-30