||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.
||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.
||Pub. in Carcinogenesis, v15 n10 p2225-2231 Oct 94. See also PB92-150762. Prepared in cooperation with Integrated Lab. Systems, Research Triangle Park, NC. and Mainz Univ. (Germany, F.R.). Inst. of Toxicology. Sponsored by Health Effects Research Lab., Research Triangle Park, NC. Carcinogenesis and Metabolism Branch.