Hepatic DNA adducts and production of mutagenic urine in 2,6-dinitrotoluene-treated B6C3F1 male mice

Cancer Letters
S E GeorgeS H Warren

Abstract

The hepatocarcinogen 2,6-dinitrotoluene (2,6-DNT) is an intermediate in the chemical synthesis of 2,4,6-trinitrotoluene and polyurethane products and can contaminate the waste stream emitted by these industries. In this study, the production of mutagenic urine metabolites and the formation of hepatic DNA adducts is examined in the B6C3F1 male mouse. Animals were administered 50 mg/kg 2,6-DNT by gavage for 3 consecutive days. No body or liver weight effects were observed in treated animals. Following sacrifice, the livers were excised and DNA isolated for examination of 2,6-DNT-derived DNA adducts. During 2,6-DNT treatment, urine was collected, concentrated, and tested for mutagenicity in the Salmonella reversion bioassay. Mutagenic urine metabolites (469+/-53 revertants/ml urine) were excreted from B6C3F1 mice treated with 2,6-DNT and were comparable to results obtained for CD-1 mice and Fischer 344 rats. Two distinct hepatic DNA adducts (0.8+/-0.1 and 0.6+/-0.1 RAL/10(8) nucleotides) were detected in B6C3F1 mice by (32)P-postlabeling and thin layer chromatography which differed from the four adducts observed in hepatic DNA from 2,6-DNT-treated Fischer 344 rats.

References

Jan 1, 1989·Teratogenesis, Carcinogenesis, and Mutagenesis·D M DeMariniJ Lewtas
Jan 1, 1989·Environmental and Molecular Mutagenesis·R W WilliamsL Claxton
Jan 1, 1986·Toxicology and Applied Pharmacology·R DixitG D Stoner
Nov 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·R C Gupta
Dec 1, 1981·Mutation Research·D B CouchD J Abernethy
Jan 1, 1982·Mutation Research·D J Abernethy, D B Couch

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