Document Detail

Comparison of DNA adduct formation between 2,4 and 2,6-dinitrotoluene by 32P-postlabelling analysis.
MedLine Citation:
PMID:  1482286     Owner:  NLM     Status:  MEDLINE    
Using 32P-postlabelling, we examined DNA binding by 2,4 and 2,6-dinitrotoluene (DNT) in Fischer-344 rats. DNA binding between the two compounds was compared to determine if differences in adduct formation and persistence could partly explain the known isomer-specific hepatocarcinogenicity of DNTs. The differences in cytotoxicity between the two isomers were also assessed. Both 2,4 and 2,6-DNT induced adduct formation in hepatic DNA. Three distinct adducts were detected following single i.p. administration of 2,4-DNT, while the 2,6-isomer produced four different adducts. Depending on the concentration administered, the two compounds differed in their relative yields. 2,6-DNT produced a greater total adduct yield relative to the 2,4-isomer at low concentrations. Following administration of high concentrations, however, 2,4-DNT predominated. The maximum adduct levels measured were 3.0 and 1.8 adducted nucleotides per 10(6) nucleotides for 2,4 and 2,6-DNT, respectively. Substantial amounts of adducts from both compounds were found to persist over time. After 2 weeks, the mean persistence for 2,4 and 2,6-DNT induced adducts were 42% and 46%, respectively. Qualitative examination for liver toxicity showed 2,6-DNT to be more cytotoxic, inducing extensive hemorrhagic centrilobular necrosis. Rats treated with 2,4-DNT did not show any observable signs of hepatocellular necrosis. Under the conditions of this study, the differences between 2,4 and 2,6-DNT in adduct formation and persistence do not appear to be sufficient to account for their differences in carcinogenicity. The toxicity of 2,6-DNT may be a determining factor in the potent carcinogenicity observed with this compound.
D K La; J R Froines
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Archives of toxicology     Volume:  66     ISSN:  0340-5761     ISO Abbreviation:  Arch. Toxicol.     Publication Date:  1992  
Date Detail:
Created Date:  1993-02-05     Completed Date:  1993-02-05     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0417615     Medline TA:  Arch Toxicol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  633-40     Citation Subset:  IM    
Department of Environmental Health Sciences, School of Public Health, University of California, Los Angeles 90024.
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MeSH Terms
Carcinogens / metabolism*
Chromatography, Thin Layer
DNA / metabolism*
Dinitrobenzenes / metabolism*
Drug-Induced Liver Injury / pathology
Liver / metabolism
Phosphorus Radioisotopes / diagnostic use
Rats, Inbred F344
Reg. No./Substance:
0/Carcinogens; 0/Dinitrobenzenes; 0/Phosphorus Radioisotopes; 121-14-2/2,4-dinitrotoluene; 606-20-2/2,6-dinitrotoluene; 9007-49-2/DNA

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