EFFECT OF PHENOBARBITAL AND HALOGENATED HYDROCARBONS ON NITROSAMINE CARCINOGENESIS

The administration of phenobarbital and halothane or methoxyflurane is known to lead to liver enlargement and enzymatic and fine structural changes characteristic for each substance. These agents chronically applied to albino mice show no carcinogenic effect. They influence however the carcinogenic effect of diethylnitrosamine. Phenobarbital increases the total dosage of DENA needed to cause death by tumor-induction as well as the survical time by 20%. The number of malignant tumors in the liver is reduced by 26%. Tumors fail to develop in organs which are reached first by the orally applied drugs after their passage through the liver. The tumors localize predominately in the stomach which shows 70% carcinomas (DENA 37%). The survival time, tumor frequency and tumor localization induced by DENA are not altered by halothane and methoxyflurane. The drugs differ, however, in the type of tumor induced. DENA alone induces hemangioendotheliomas and liver cancers in a ratio of 26:1. The administration of halothane changes the ratio to 2:1. Methoxyfluorane leads to a clear predominance of epitheliomas to endotheliomas with a ratio of 0.6:1. The total dosage of DENA is increased by 7-9%, perhaps due to the preferential induction of liver epithelial tumors which do not lead to early death through hemorrhage. © 1969 Springer-Verlag.