SYNERGISTIC EFFECTS OF PHENOBARBITAL AND THIOUREA ON PROLIFERATIVE LESIONS IN THE RAT-LIVER

To evaluate the effects of phenobarbital (PB) and thiourea (TU), alone or in combination, on proliferative lesions of the liver, thyroid and lung, male F344 rats initiated with 2000 mg/kg body weight N-bis(2-hy droxypropyl) nitrosamine (DHPN) were given diet and/or drinking water containing 0% PB/TU (group 1), 1000 ppm PB (group 2), 0.1% TU (group 3 ) and 500 ppm PB and 0.05% TU (group 4), from weeks 2 to 20 for 19 wee ks. Group 4 showed remarkable increases in the number of hepatocellula r altered foci per animal, the values being superior to the averages o f groups 2 and 3. The number of thyroid proliferative lesions per anim al was highest in group 3 and lowest in group 2. Lung proliferative le sions were induced in all groups, but no modifying influence on their development was evident in the combined group. The present results ind icate that combined administration of PB and TU exerts synergistic enh ancing effects on hepatocarcinogenesis.