Preneoplastic lesions and DNA adduct formation of the airborne genotoxic agents 2-nitrofluorene and 2,7-dinitrofluorene.

L Möller, X S Cui, U B Torndal, L C Eriksson

Index: Carcinogenesis 14(12) , 2627-32, (1993)

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Abstract

The urinary mutagenicity (unconjugated forms) after administration of 2,7-dinitrofluorene (2,7-dNF) orally or i.p. was lower compared to 2-nitrofluorene (NF) administration. When partial hepatectomy (PH) was performed before i.p. administration, both substances had higher excretion of mutagens in which 2,7-dNF increased dramatically and showed a higher level of mutagenicity compared to NF. NF and 2,7-dNF formed DNA adducts in liver tissue. By different routes of administration (oral or i.p.) of the same substance at the same dose (200 mg/kg body wt), the patterns of DNA adducts were different. It seemed to be that PH, which was performed 18 h before i.p. administration, had no significant effects on the amount of DNA adducts. Generally, the total amount of DNA adducts after oral administration was higher compared to i.p. administration. Dramatic increases of the nitroreduced DNA adducts were noticed after oral compared to i.p. administration. When given i.p., both substances showed initiating capacity in foci formation both at 50 mg/kg body wt and 200 mg/kg body wt. When NF and 2,7-dNF were administered orally by single gavage, 2,7-dNF was more potent as an initiator in foci formation compared to NF and the initiating capacity of the two substances was higher compared to i.p. administration. The great difference between these two nitro-PAHs seen in the bacterial tests for mutagenicity was not seen in the in vivo genotoxic experiments. The results indicate that both NF and 2,7-dNF formed DNA adducts and preneoplastic lesions after both i.p. and oral administration. After oral administration, both substances were more potent in causing DNA adduct and foci formation compared to i.p. administration. 2,7-dNF was more potent as an initiator than NF especially after oral administration. The urinary excretion of unconjugated mutagens did not indicate the genotoxic effects of the parent substance.