Modifying effects of a single injection of phenobarbital on the inhibitory action of benzo(a)pyrene on 3H-thymidine incorporation into various organs of the mouse.

The effects of the procarcinogen benzo(a)pyrene and the enzyme inducer phenobarbital on the DNA turnover in various organs of male C57BL mice were evaluated by measuring the incorporation of [6-3H]thymidine. When injected intraperitoneally 48 h before sacrifice, benzo(a)pyrene (28.8 mg/kg body weight) inhibited the incorporation of 3H-thymidine into the spleen, thymus, testis, and small intestine. A corresponding analysis with phenobarbital sodium (75 mg/kg b.w.) revealed reduced incorporation of 3H-thymidine into the pancreas (after 24 h) and bone marrow (after 72 h). The effects of combining benzo(a)pyrene and phenobarbital was examined by injecting the latter agent either 24 h before or after the polycyclic hydrocarbon. A previous injection of phenobarbital resulted in a potentiation of the inhibitory action of benzo(a)pyrene in the spleen. However, when phenobarbital was given after benzo(a)pyrene, there was a five-fold increase of the 3H-thymidine incorporation into the liver in comparison to the controls given vehicle. The demonstration that a single injection of phenobarbital has modifying effects on the 3H-thymidine incorporation both when administered alone and in combination with benzo(a)pyrene indicates that enzyme inducers may influence the outcome in genotoxicity tests.