COMPARATIVE TUMOR-PROMOTING ACTIVITIES OF PHENOBARBITAL, AMOBARBITAL, BARBITAL SODIUM, AND BARBITURIC-ACID ON LIVERS AND OTHER ORGANS OF MALE F344/NCR RATS FOLLOWING INITIATION WITH N-NITROSODIETHYLAMINE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 74  (2) , 509-516
Abstract
Tumor-promoting abilities of 4 barbiturates, phenobarbital [(PB) CAS: 50-06-6], amobarbital [(AB) CAS:57-43-2], barbital sodium [(BB) CAS: 144-02-5], and barbituric acid [(BA) CAS:67-52-7], on the development of neoplasms in livers and other organs of rats following initiation with N-nitrosodiethylamine [(DENA) CAS: 55-18-5] were compared. Four wk old F344/NCr male rats were given a single i.p. injection of 75 mg DENA/kg body wt. Beginning 2 wk later they were given either tap water (group 1) of drinking water containing 500 ppm of PB (group 2), the sodium salt of BB (group 3), AB (group 4), or BA (group 5) for the remaining experimental period. Control groups (groups 6-10) received an i.p. injection of saline alone and 2 wk later were given either tap water or drinking water containing barbiturates as listed above. Animals were sacrificed at either 52 wk or 78 wk. None of the barbiturates altered the growth and survival of animals. PB and BB increased liver wt and significantly enhanced the development of hepatocellular foci and hepatocellular adenomas at 52 wk and hepatocellular loci, hepatocellular adenomas and trabecular carcinomas at 78 wk in DENA-treated rats. No such enhancing effects were observed with AB or BA. PB or BB did not significantly enhance the incidence of nonhepatic tumors at 52 wk. At 78 wk BB significantly enhanced the development of renal tubular adenomas and carcinomas, while PB enhanced the development of thyroid follicular cell neoplasms in DENA-treated rats. Apparently, barbiturates exhibited structure-promoting activity relationships, their promoting abilities evidently were not restricted to liver alone. Substitution of both hydrogen atoms at the C-5 position of the pyrimidine ring by alkyl or aryl groups appears to be essential but not sufficient for tumor-promoting activity of barbiturates.