Toxicological characterization of a novel in vivo benzo[a]lpyrene metabolite, 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid anhydride
2002 (English)In: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 15, no 10, 1274-1280 p.Article in journal (Refereed) Published
Recently, we described a new in vivo pathway in the metabolism of benzo[a]pyrene (BP) that involves an opening of the aromatic ring system. One of the products of this pathway, isolated from rat urine, was the anhydride of 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid (ABADA). We have now investigated the effect of ABADA on several cellular targets, known to be important in tumor formation. ABADA was as efficient as BP-7,8-diol-9,10-epoxide in inducing direct strand breaks but not alkali labile sites in DNA in HT-29 cells and exhibited weak mutagenic activity in Salmonella typhimurium strain TA 102. The cytotoxicity of ABADA to HCT 116 cells appeared to be due to apoptosis, as caspase-3 activity and poly-ADP-ribose polymerase (PARP) cleavage was observed. COX-2 promoter activity was induced by ABADA in HCT 116 cells. In conclusion, this novel metabolic pathway may also be contributing to the carcinogenicity of BP.
Place, publisher, year, edition, pages
2002. Vol. 15, no 10, 1274-1280 p.
IdentifiersURN: urn:nbn:se:sh:diva-15783DOI: 10.1021/tx0255491ISI: 000178807800010PubMedID: 12387625ScopusID: 2-s2.0-0036801420OAI: oai:DiVA.org:sh-15783DiVA: diva2:508471