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

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...

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Published in:Carcinogenesis (New York) 1993-12, Vol.14 (12), p.2627-2632
Main Authors: MÖller, L., Cui, X.-S., Torndal, U.-B., Eriksson, L.C.
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Cui, X.-S.
Torndal, U.-B.
Eriksson, L.C.
description 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.
doi_str_mv 10.1093/carcin/14.12.2627
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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. 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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.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>8269636</pmid><doi>10.1093/carcin/14.12.2627</doi><tpages>6</tpages></addata></record>
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ispartof Carcinogenesis (New York), 1993-12, Vol.14 (12), p.2627-2632
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source Oxford University Press:Jisc Collections:Oxford Journal Archive: Access period 2024-2025
subjects Animals
Biological and medical sciences
Chemical mutagenesis
DNA Damage
Fluorenes - toxicity
Liver Neoplasms - chemically induced
Liver Neoplasms - genetics
Male
Medical sciences
Mutagens - toxicity
Precancerous Conditions - chemically induced
Precancerous Conditions - genetics
Rats
Rats, Wistar
Toxicology
title Preneoplastic lesions and DNA adduct formation of the airborne genotoxic agents 2-nitrofluorene and 2, 7-dinitrofluorene
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