Effects of piperonyl butoxide on the toxicity and hepatocarcinogenicity of 2-acetylaminofluorene and 4-acetylaminobiphenyl, and their n-hydroxylated derivatives, following administration of newborn mice.
Neonatal ICR/Ha mice were injected subcutaneously with a single dose of 25, 50 and 100 microgram of 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 microgram of 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.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives / Q000633:toxicity*; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000611:Aminobiphenyl Compounds / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002273:Carcinogens / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005449:Fluorenes / Q000633:toxicity*; D006877:Hydroxamic Acids / Q000633:toxicity; D006900:Hydroxylation; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D010882:Piperonyl Butoxide / Q000494:pharmacology*; D012737:Sex Factors
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D005449:Fluorenes; D006877:Hydroxamic Acids; C001365:N-hydroxy-4-acetylaminobiphenyl; D015127:9,10-Dimethyl-1,2-benzanthracene; D015073:2-Acetylaminofluorene; D010882:Piperonyl Butoxide; C020853:4-acetylaminobiphenyl