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Main Title Morphological Transformation and DNA Adduct Formation by Dibenz(a,h)anthracene and Its Metabolites in C3H10T1/2CL8 Cells.
Author Nesnow, S. ; Ross, J. ; Beck, S. ; Lasley, J. ; Nelson, G. ;
CORP Author Environmental Health Research and Testing, Inc., Research Triangle Park, NC. ;Integrated Lab. Systems, Research Triangle Park, NC. ;Mainz Univ. (Germany, F.R.). Inst. of Toxicology.;Health Effects Research Lab., Research Triangle Park, NC. Carcinogenesis and Metabolism Branch.
Publisher cOct 94
Year Published 1994
Report Number EPA-68-D1-0148; EPA/600/J-94/531;
Stock Number PB95-148938
Additional Subjects DNA adducts ; Toxicology ; Neoplastic cell transformation ; Mutagens ; Cultured cells ; C3H inbred mice ; Fibroblasts ; Metabolism ; Metabolic activation ; Reprints ; Dibenz(a) ; h)anthracene
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NTIS  PB95-148938 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. NTIS 03/06/1995
Collation 10p
Abstract
Dibenz(a,h)anthracene (DB(a,h)A) has been studied to identify the major routes of metabolic activation in transformable C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts in culture. The morphological transforming activities of three potential intermediates formed by metabolism of DB(a,h)A by C3H10T1/2 cells, trans-3,4-dihydroxy-3,4-dihydro-DBA (DBA-3,4-diol), anti-trans-3,4-dihydroxy-3,4-dihydro-DBA-1,2-oxide (DBA-3,4-diol-1,2-oxide), and DBA-5,6-oxide were determined. DBA-3,4-diol-1,2-oxide was a strong morphological transforming agent giving 73% dishes with Type II or III foci at 0.5 micrograms/ml. DBA-3,4-diol and DB(a,h)A had similar activities, approximately 24-42% dishes with Type II or III foci at 2.4 micrograms/ml. DBA-5,6-oxide, was found to be inactive. DNA adducts of DB(a,h)A, DBA-3,4-diol, DBA-3,4-diol-1,2-oxide, and DBA-5,6-oxide in C3H10T1/2 cells were isolated, separated, and quantitated using the (32)P-postlabeling method. Qualitatively, all of the DNA adducts observed in C3H10T1/2 cells treated with DB(a,h)A were also observed in the DNA of these cells treated with DBA-3,4-diol. These results indicate that DB(a,h)A is metabolically activated through DBA-3,4-diol in C3H10T1/2 cells. Of the DNA adducts formed, 86% are a result of the further metabolism of DBA-3,4-diol to DBA-3,4-diol-1,2-oxide. These studies provide little evidence for the metabolism of DB(a,h)A by the K-region pathway.