HUMAN NAD(P)H-QUINONE OXIDOREDUCTASE INDUCTION IN HUMAN HEPATOMA-CELLS AFTER EXPOSURE TO INDUSTRIAL ACRYLATES, PHENOLICS, AND METALS

Induction of the endogenous human NAD(P)H:quinone oxidoreductase (HQOR (1)) gene in the human hepatoma cell line HepG(2) was measured at both the enzyme activity and RNA levels after exposure to a variety of ind ustrial compounds. An RNA probe was designed that was complementary to portions of both the coding region and the 3'-nontranslated region un ique to the largest (2.7-kilobase) HQOR, transcript. Induction by thre e strong inducers of HQOR, verified the utility of the antisense RNA p robe. Ten industrial chemicals were evaluated as potential inducers, i e. acrylonitrile, Sb2O3, BaO, CdCl2, CuCl, ethyl acrylate, methyl acry late, MoO3, phenol, and toluene. Induction at the RNA level was about 2-fold higher than at the enzyme activity level except in the case of acrylonitrile, for which induction at the enzyme activity and RNA leve ls was similar. There was no preferential induction of the 2.7-kilobas e transcript for any chemical tested, including 2,3,7,8-tetrachloro-di benzo-p-dioxin, which had previously been reported to preferentially i nduce this transcript Six of the 10 industrial chemicals, including fo ur previously untested chemicals (phenol, Sb2O3, CuCl, and MoO3), were found to induce the HQOR, gene. By comparison, previous studies in ro dent systems failed to accurately predict the human HQOR, gene respons e. Two chemicals previously shown to be inducers in rodent systems (me thyl acrylate and CdCl2) failed to induce the HQOR, gene. These result s emphasize the importance of analyzing induction of the endogenous hu man gene, rather than simply extrapolating from rodent systems or gene fusion experiments.