Decreased toxicity of dimethylnitrosamine in rats after treatment with carbon tetrachloride

Abstract

A non-lethal dose of carbon tetrachloride (CCl4), that produced necrosis in the liver followed by regeneration, protected rats from the toxic effects of dimethylnitrosamine (DMN), for a period lasting between 48 and 60 h. At 42 h, when DNA synthesis was at a maximum, the LD50 of DMN was increased from 27.2 to 42.5 mg/kg.After CCl4, the level of DMN-demethylase in the liver fell sharply by 6 h, maintained a low level for a period lasting between 42 and 60 h, and returned to normal by 72 h. No change occurred in the level of the DMN-demethylase in the kidney.When DMN was given 42 h after CCl4, the acute cellular changes and necrosis usually produced were not superimposed on the lesions produced by the CCl4 but when the interval was 60 h, acute necrosis was again produced in the liver. On the other hand the minor degree of necrosis in the distal convoluted tubules of the kidneys produced by DMN was much increased when it was administered 42 h after a dose of CCl4 but not when given after 60 h.