title: Promotion by sodium barbital of renal cortical and transitional cell tumors, but not intestinal tumors, in F344 rats given methyl(acetoxymethyl)nitrosamine, and lack of effect of phenobarbital, amobarbital, or barbituric acid on development of either renal or intestinal tumors.
abstract: 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.
authors.affiliation: Biological Carcinogenesis & Development Program, Program Resources, Inc., Frederick Cancer Research Facility, MD.
authors.forename: B A
authors.initials: BA
authors.lastname: Diwan
authors.forename: M
authors.initials: M
authors.lastname: Ohshima
authors.forename: J M
authors.initials: JM
authors.lastname: Rice
mesh_terms: D000236:Adenoma / Q000139:chemically induced*; D000654:Amobarbital / Q000633:toxicity*; D000818:Animals; D001462:Barbital / Q000633:toxicity*; D001463:Barbiturates / Q000633:toxicity*; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced*; D002292:Carcinoma, Renal Cell / Q000139:chemically induced; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced; D003043:Cocarcinogenesis; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000633:toxicity; D007414:Intestinal Neoplasms / Q000139:chemically induced*; D007680:Kidney Neoplasms / Q000139:chemically induced*; D008113:Liver Neoplasms / Q000139:chemically induced; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013964:Thyroid Neoplasms / Q000139:chemically induced
chemical_list: D001463:Barbiturates; D002273:Carcinogens; C014659:methyl(acetoxymethyl)nitrosamine; D001462:Barbital; D000654:Amobarbital; D004128:Dimethylnitrosamine; C032232:barbituric acid; D010634:Phenobarbital