Antioxidant prevention of tumor promoter induced inhibition of mouse hepatocyte intercellular communication

Abstract

The liver tumor promoters, phenobarbital (20–500 μg/ml), lindane (1,2,3,4,5,6-hexachlorocyclohexane, γ-isomer; 0.1–5.0 μg/ml), and DDT (1,1-bis[4-chlorophenyl]-2,2,2-trichloroethane; 0.5–10.0 μg/ml), and the hydrogen peroxide-generating enzyme, glucose oxidase (0.01–0.10 units/ml) inhibited gap junctional intercellular communication between B 6C 3F 1 mouse hepatocytes in primary culture. Addition of the antioxidants, superoxide dismutase (100 units/ml), DPPD ( N,N′-diphenyl-1,4-phenylenediamine; 25 μM), and vitamin E ( dl-α-tocopherol acetate; 100 μM), to tumor promoter-treated cultures prevented the inhibition of hepatocyte intercellular communication. DPPD and vitamin E, prevented the inhibition of hepatocyte intercellular communication by glucose oxidase. Superoxide dismutase had no effect on the inhibition of intercellular communication caused by glucose oxidase. These results suggest that activated oxygen species are produced during liver tumor promoter treatment of cultured mouse hepatocytes and are responsible for the inhibition of mouse hepatocyte intercellular communication by the promoters.