Methylated derivatives of pyrene and fluorene: evaluation of genotoxicity in the hepatocyte/DNA repair test and tumorigenic activity in newborn mice.
The genotoxicity of 1-methylpyrene, 1,6-dimethylpyrene, 1-methylfluorene, 9-methylfluorene, and 1,9-dimethylfluorene was evaluated in the hepatocyte primary culture/DNA repair test, and the tumorigenic potency of these compounds was tested by bioassay in newborn mice. With the exception of 1-methylfluorene, all of these methylated polycyclic aromatic hydrocarbons are known mutagens in Salmonella typhimurium. Both 1-methylpyrene and 1,6-dimethylpyrene induced unscheduled DNA synthesis in rat hepatocytes. However, only 1-methylpyrene was tumorigenic when administered to newborn male mice. None of the methylated fluorenes assayed in the hepatocyte primary culture/DNA repair test induced unscheduled DNA synthesis. While 1,9-dimethylfluorene exhibited weak tumorigenic activity when administered by subcutaneous injection to newborn mice, 1-methylfluorene and 9-methylfluorene were inactive.
D000818:Animals; D000831:Animals, Newborn; D004247:DNA / Q000096:biosynthesis*; D004260:DNA Repair / Q000187:drug effects*; D005260:Female; D005449:Fluorenes / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D009153:Mutagens; D011721:Pyrenes / Q000633:toxicity*
D005449:Fluorenes; D009153:Mutagens; D011721:Pyrenes; C030637:1,9-dimethylfluorene; C053036:1-methylfluorene; C053034:1,6-dimethylpyrene; D004247:DNA; C030636:9-methylfluorene; C053035:1-methylpyrene