Effects of Piperonyl Butoxide on the Toxicity and Hepatocarcinogenicity of 2-Acetylaminofluorene and 4-Acetylaminobiphenyl, and Their N-Hydroxylated Derivatives, following Administration to Newborn Mice

Abstract

Neonatal ICR/Ha mice were injected subcutaneously with a single dose of 25, 50, and 100 μgof 4-acetylaminobiphenyl (AAB), N-hydroxy-4-acetylaminobiphenyl (N-OH-AAB), 2-acetylaminofluorene (AAF), or N-hydroxy-2-acetylaminofluorene (N-OH-AAF) alone or together with 2.5% piperonyl butoxide (PB) in tricaprylin; negative control groups were injected with tricaprylin, and positive control groups were injected with 30 μgof 7,12-dimethylbenz(a)anthracene (DMBA), alone or with PB. PB induced synergistic toxicity in the various groups of mice injected with the nonhydroxylated and hydroxylated amine carcinogens, or with DMBA, as compared with groups injected with carcinogen alone. AAB, N-OH-AAB, AAF, and N-OH-AAF all induced dose-related hepatocarcinogenicity in male, but not female mice, which was not consistently influenced by concomitant administration of PB. DMBA control groups developed pulmonary adenomas and lymphomas in both sexes, and hepatomas in males, whose incidences were not modified by PB.