Preneoplastic lesions, DNA adduct formation and mutagenicity of 5-, 7- and 9-hydroxy-2-nitrofluorene, metabolites of the air pollutant 2-nitrofluorene.
The metabolites of 2-nitrofluorene (NF), 5-, 7- and 9-OH-2-nitrofluorene (OH-NF) were compared for their genotoxicity. Seventy-two hours after intraperitoneal administration of these substances individually to rats (100 mg/kg body wt.), DNA adducts in liver tissue were analyzed with 32P-TLC and 32P-HPLC. An in vivo liver model was used to test the initiating capacity of the said substances for the formation of preneoplastic lesions. 5-OH-NF showed low capacity to induce DNA adduct formation and low potential as initiator to induce preneoplastic lesions-foci/nodules in the liver of rats. Both 7- and 9-OH-NF induced DNA adducts and preneoplastic liver lesions but with smaller quantities compared to NF. It seems that 7- and 9-OH-NF can not be considered as detoxification products of NF. In general, the initiating capacity of these substances for the formation of preneoplastic lesions has a good correlation with their potency to form DNA adducts.
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X S
XS
Karolinska Institute, Department for Biosciences, Huddinge, Sweden.
Bergman
J
J
Möller
L
L
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D015197:Carcinogenicity Tests; D018736:DNA Adducts; D005449:Fluorenes / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000473:pathology; D009152:Mutagenicity Tests; D011230:Precancerous Conditions; D051381:Rats
D000393:Air Pollutants; D018736:DNA Adducts; D005449:Fluorenes; C019499:2-nitrofluorene