title: Induction of sister chromatid exchanges by benzidine in rat and human hepatoma cell lines and inhibition by indomethacin.
abstract: The genotoxic activity of benzidine was studied in two cell lines derived from rat (H4) and human (HepG2) hepatomas which have been shown to be capable of activating certain promutagens. The responses were compared to results in two lung-derived fibroblast lines (IMR-90 and V79) which appear to have little or no metabolizing capability. Benzidine was found to induce sister chromatid exchanges in the two liver-derived cell lines in a dose-dependent fashion but failed to induce sister chromatid exchanges in the fibroblast lines. Since one proposed pathway for benzidine activation involves prostaglandin-mediated metabolism, we tested the effect of pretreatment with indomethacin, an inhibitor of this metabolic pathway. Indomethacin was highly effective in inhibiting benzidine-induced sister chromatid exchanges in both H4 and HepG2 cells. These results suggest that some DNA damage may occur in the livers of fast acetylating species such as the rat without prior N-acetylation and that some amount of DNA damage may occur in the livers of slow acetylating species, even when the liver is not the target organ for carcinogenesis.
authors.affiliation: Department of Radiology, George Washington School of Medicine and Health Sciences, Washington, DC.
authors.forename: M K
authors.initials: MK
authors.lastname: Grady
authors.forename: D
authors.initials: D
authors.lastname: Jacobson-Kram
authors.forename: K L
authors.initials: KL
authors.lastname: Dearfield
authors.forename: J R
authors.initials: JR
authors.lastname: Williams
mesh_terms: D000818:Animals; D001560:Benzidines / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D001560:Benzidines; C029876:benzidine; D007213:Indomethacin