TRANSCRIPTIONAL ACTIVITY OF QUINONE METHIDES DERIVED FROM THE TUMOR PROMOTER BUTYLATED HYDROXYTOLUENE IN HEPG2 CELLS

Butylated hydroxytoluene (BHT) is a pulmonary toxin and tumor promoter in mice presumably due to the formation of two quinone methides (QMs) that alkylate cellular nucleophiles. The activation of stress genes b y these electrophilic metabolites was investigated with an assay syste m consisting of 14 recombinant cell lines derived from the human hepat oma line HepG2, each carrying a unique promoter or response element co nstruct fused to the reporter gene for chloramphenicol acetyl transfer ase (CAT). The largest responses to QMs occurred in cells containing e ither the metallothionein IIA, glutathione S-transferase Ya, or 70 kDa heat shock protein promoter, or the xenobiotic response element. The other cell lines exhibited only small or no effects. These results are consistent with transcriptional activities reported for several other electrophiles known to undergo covalent interactions with proteins. ( C) 1998 Elsevier Science Ireland Ltd. All rights reserved.