Protection by a small dose of carbon tetrachloride against the toxic effects of dimethylnitrosamine in rats

A single intragastric dose of carbon tetrachloride (CCl₄) (0.01-2.5 ml/kg protected male Sprague Dawley rats against the toxic effects of dimethylnitrosamine (DMN). This appeared to be due to the reduction in the levels of DMN demethylase, a microsomal enzyme involved in the metabolism of DMN. The increase in the LD₅₀ of DMN and the reduction in demethylase levels were observed within 20 min of dosing the CCl₄. The changes were maximal by 12 hr, persisted until 48 hr and began to recover between 48 and 60 hr. The LD₅₀ of DMN and the level of DMN demethylase returned to normal between 120 and 144 hr. Carbon tetrachloride also prevented the development of the hepatocellular necrosis which normally follows the administration of toxic doses of DMN.