Biochemical and genetic analysis of variant mouse hepatoma cells defective in the induction of benzo(a)pyrene-metabolizing enzyme activity

Abstract

We have analyzed wild type mouse hepatoma (Hepa 1c1c7) cells and variant cells which are defective in the induction of benzo(a)pyrene-metabolizing enzyme activity. One type of variant has no detectable basal or inducible aryl hydrocarbon hydroxylase activity. This class contains apparently normal cytosolic receptors for 2,3,7,8-tetrachlorodibenzo-p-dioxin, but is unable to translocate the inducer-receptor complex to the nucleus. The second type of variant has low levels of basal and inducible aryl hydrocarbon hydroxylase activity. This class contains cytosolic receptors which are decreased either in their number or in their ability to bind 2,3,7,8-tetrachlorodibenzo-p-dioxin; translocation of the inducer-receptor complex to the nucleus is apparently normal. Cell fusions indicate that both variant phenotypes are recessive with respect to wild type. Complementation analyses indicate that the defects are located on different genes.