Reciprocal Relationship Between the Production of Adrenal Damage by 7,12-Dimethylbenz(a)anthracene in Rats and the Induction of Liver Damage by Various Treatments

Abstract

Further investigations into the mechanism by which CCl₄ administration to Sprague-Dawley rats protects them against the adrenocorticolytic action of dimethylbenz(a)anthracene (DMBA) are reported. The results show that CCl₄ must be given shortly before DMBA to achieve the best protection and that treatments given after DMBA are ineffective. It was established that the hepatotoxicity of CCl₄ in these experiments was related reciprocally to the adrenocorticolytic effect of DMBA.

Protection with butter yellow (DAB) was achieved only when sufficient time elapses for drug metabolism to be stimulated in the liver. Butter yellow given after DMBA has no protective effect but the prior exposure of the rats to DMBA potentiates the hepatotoxic effects of DAB.

Partial hepatectomy gives protection when performed 1 day before DMBA; shorter intervals give no protection. Some protection can be achieved with resection 6 or 24 hours after DMBA.