Partial hepatectomy and toxicity of dimethylnitrosamine and carbon tetrachloride, in relation to the carcinogenic action of dimethylnitrosamine

The yield of tumors in the liver of rats was increased when dimethyl nitrosamine (DMN) was given 1, 6 or 12 h after partial hepatectomy and still further increased if it was given after an interval of 24-72 h. The increase was greater after two thirds than after one third hepatectomy. An increase in the number of kidney tumors was also found. Microsomal DMN demethylase activity was depressed after partial hepatectomy for up to 6 days in mice and rats. The LD₅₀ DMN on the other hand was decreased for 3 days, after which it returned to normal. The extent of liver necrosis produced by DMN was increased at 6 and 24 h after partial hepatectomy but was within the usual range at longer intervals. These results suggest that prolonged exposure of the tissues to DMN after partial hepatectomy played a significant role in the development of liver tumors as well as those in the kidney, in addition to the role of regeneration of the liver, and that the relative roles are still to be elucidated.