Partial hepatectomy and toxicity of dimethyl-nitrosamine and carbon tetrachloride, in relation to the carcinogenic action of dimethylnitrosamine.

The yield of tumours in the liver of rats was increased when dimethylnitrosamine 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 tumours was also found. Microsomal DMN-demethylase activity was depressed after partial hepatectomy for up to 6 days in mice and rats. The LD50 of 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 tumours as well as those in the kidney, in addition to the role of regeneration of the liver, and that the relative roles were still to be elucidated.