Reciprocal modifying effects of isomeric forms of aminophenol on induction of neoplastic lesions in rat liver and kidney initiated by N-ethyl-N-hydroxyethylnitrosamine.

The effects of four isomeric forms of aminophenols, ortho-, meta-, para-aminophenol and acetaminophen (o-, m-, p-AP and AAP, respectively) on liver and kidney carcinogenesis initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN) were tested. Rats were given 0.1% EHEN (in their drinking water for 2 weeks) and then diet containing these compounds at concentrations of 0.8% for 49 weeks. Administration of o-AP and AAP significantly decreased the number and area of preneoplastic foci staining immunohistochemically for glutathione S-transferase placental type (GST-P) per unit area of liver section as compared with the values for rats given EHEN alone. o-AP and AAP also significantly decreased the incidence of hepatocellular carcinoma. In contrast, p-AP and AAP significantly increased quantitative values for kidney preneoplastic lesions and renal cell adenoma. It is suggested that the cytotoxic effects of these chemicals preferentially suppressed the proliferation of preneoplastic liver cells, but stimulated the mitotic activity of preneoplastic tubular lesions in the kidney.