Enhancement of urinary bladder tumorigenesis in hamsters by coadministration of 2-acetylaminofluorene and indole.

Hamsters treated with 2-acetylaminofluorene (AAF) were studied to test the effects of dietary indole and excess DL-tryptophan and the initial age of the animals on the development of bladder tumors. Neonatal males and females were given i.p. injections of AAF, 5 mg/100 g body weight, 3 times weekly until weaning. They were then fed a synthetic diet containing AAF with or without 1.6% indole or 2.0% DL-tryptophan. Enhancement of tumorigenesis in the urinary bladder was evident only when indole was added to the diet containing a low dose of AAF (0.03%). Twenty-four of 27 hamsters fed the combination diet for 10 months developed tumors (89%); 20 of them were invasive. On the other hand, 13 of 26 on the diet containing AAF alone developed bladder tumors (50%); 8 of them were invasive. The difference in incidence was significant (p<0.01). Development of bladder tumors appeared slightly delayed when older hamsters (initially 4 weeks old) were used, but after 11 months all animals developed bladder tumors. As was observed in rats, added indole or tryptophan protected the liver from AAF injury and greatly reduced the development of cholangiocarcinomas.