INDUCTION OF RAT HEPATIC WEIGHT GAIN AND FUNCTIONAL CAPACITY BY BARBITURATES: CORRELATION WITH TUMOR-PROMOTING ABILITY

A series of barbiturates administered for $\sim$2 weeks in the drinking water (amobarbital, barbituric acid, hexobarbital, sodium barbital, sodium pentobarbital and sodium phenobarbital) or in the diet (allobarbital, aprobarbital, 5-ethylbarbituric acid, phenobarbital and 5-phenylbarbituric acid) were examined for their ability to induce liver weight gain and functional capacity in the male F344 rat. A tumor-promoting potency index was assigned to the barbiturates based upon published in vivo data. Correlation statistics were generated for tumor-promoting ability vs alkoxyresorufin O-dealkylase, p-nitroanisole O-demethylase, epoxide hydrolase and quinone oxidoreductase activity and liver-to-body weight ratio increase, duration of sedative action, pKa and lipophilicity coefficient. With the exception of pKa and lipophilicity coefficient, all parameters correlated highly with tumor-promoting ability, suggesting that tumor-promotion may be a facet of the pleiotropic "phenobarbital" response exhibited by many of the barbiturates.