Genetic differences in the extent of aryl hydrocarbon hydroxylase induction in mouse fetal cell cultures.

Benz[a]anthracene induces aryl hydrocarbon hydroxylase activity in secondary fetal cell cultures derived from various inbred mouse strains. The maximally inducible level of hydroxylase activity from the C57BL/6N strain is 4 to 6 times higher than that from the DBA/ZN strain in cell cultures derived from the entire mouse fetus. There are no differences between C57BL/6N and DBA/2N cell cultures in the rate of uptake of benz[a]anthracene by the cells, in the binding of polycyclic hydrocarbon to cellular material, or in the rate of degradation of the induced hydroxylase activity. A 24-hour treatment of the cell cultures with benz[a]anthracene produces increases in the microsomal content of total protohemeand CO-bindingcytochrome (about 88% and 120%, respectively) in C57BL/6N cells compared to about 31% and 33%, respectively, in DBA/2N cells. Concomitantly, the blue spectral shift in the absorption maximum of the reduced hemoprotein-CO complex is at least 4 nm in microsomal fractions from C57BL/6N cells and between 1 and 2 nm in DBA/2N microsomes. In cells exposed to benz[a]anthracene plus cycloheximide and then grown in fresh growth medium, the rise in hydroxylase activity in C57BL/6N cells is at least 4 times greater than that from DBA/2N cells. In cells exposed to benz[a]anthracene and then treated with actinomycin D, the stimulatory phenomenon by the antibiotic is at least 4 times greater in C57BL/6N cells than that in DBA/2N cells. These experiments provide indirect evidence for a decreased expression of an induction-specific RNA in DBA/2N cells. The decreases in (a) formation of CO-binding hemoprotein, (b) spectral shift in the absorbance peak of the reduced microsomal cytochrome-CO complex, and (c) expression of induction-specific RNA may be related to the decreased extent of aryl hydrocarbon hydroxylase induction in DBA/2N cells.