Role of the Vehicle in the Genesis of Bladder Carcinomas in Mice by the Pellet Implantation Technic1

Several compounds—arachic acid, hexaethylbenzene, hexamethylbenzene, 1-octadecanol, palmitic acid, and stearamide— were individually compressed as pellets and tested, by im plantation into the mouse bladder, as possible vehicles for carcinogenicity experiments. All of these compounds were found to b3 associated with a 3-17% incidence of bladder carcinomas. Pellets of 23-methylcholanthrene (MC)2 used alone induced an incidence of 52%, whereas pallets of XAE used alone induced an incidence of 1.6%. The pallets of XAE disintegrated within 2 days following surgical introduction into the mouse bladder. When cholesterol pellets were placed in the mouse bladder and XAE was injected s.c., a 30% incidence of bladder carcinomas was observed. However, the repeated s.c. injection of XAE into mice whose bladders did not contain cholesterol pellets failed to produce any bladder carcinomas. XAE was observed to be pres ent in the urine of mice following s.c. injection. It was suggested that the prolonged presence of the vehicle in the mouse bladder had a promoting effect on the genesis of the bladder carcinomas. Several metabolites of the essential amino acid tryptophan were quantitatively measured in the urine of mice. It was found that 3-hydroxy-L-kynurenine was present in mouse urine; this had previously been demonstrated to be associated with the produc tion of a significant incidence of mouse bladder carcinomas when implanted in a cholesterol vehicle. It was postulated that the combination of continued excretion of this compound or some other metabolite in the urine and the protracted presence of a pellet resulted in the genesis of a low-background incidence of bladder carcinomas in mice.