Comparative effects of four
barbiturates,
phenobarbital (PB),
amobarbital (AB),
sodium barbital (NaBB), and
barbituric acid (BA) on the development of
neoplasms in the intestinal tract and other organs were investigated in rats following initiation with
methyl(acetoxymethyl)nitrosamine (
DMN-OAc). Four-week-old F344/NCr male rats were given a single i.p. injection of 0.05 nmol
DMN.OAc in 5 ml sterile
phosphate buffered saline/kg
body weight. Two weeks after
DMN.OAc treatment, the animals were provided with either tap water or
drinking water containing 500 p.p.m. of PB, NaBB, AB, or BA for the remaining experimental period. Control groups received a single i.p. injection of 5 ml of sterile
phosphate buffer/kg
body weight and 2 weeks later were given either tap water or
drinking water containing 500 p.p.m. of one of the
barbiturates listed above. Rats were killed at 52 weeks or 80 weeks after
DMN.OAc injection.
DMN.OAc induced multiple intestinal
tumors that occurred mostly in the mucosa of the small intestine, especially the terminal ileum. None of the
barbiturates had any effect on either incidence or multiplicity of intestinal
tumors. PB significantly enhanced the development of hepatocellular
tumors as well as thyroid follicular cell
neoplasms in
DMN.OAc initiated rats, while the subsequent administration of NaBB, but not other
barbiturates, resulted in the development of renal cortical and pelvic transitional cell
tumors. This is the first demonstration of promotion of
carcinogenesis in renal pelvic transitional epithelium, a cell type not previously recognized as vulnerable to initiation by
DMN.OAc given i.p. NaBB without prior administration of
DMN.OAc induced severe nephropathy and focal
hyperplasia of both renal cortical tubular and pelvic transitional cell epithelium. No such effects were observed with either PB, AB, or BA. Our results failed to confirm the earlier findings of others that intestinal epithelial
carcinogenesis could be promoted by continuous
oral administration of NaBB. However, these results strongly support and extend our previous conclusions that some
barbiturates have broad organ specificities and promote epithelial
carcinogenesis in more than one organ and tissue.