Ribonucleic Acid Synthesis-dependent Induction of Aryl Hydrocarbon Hydroxylase in the Absence of Ribosomal Ribonucleic Acid Synthesis and Transfer

The microsomal enzyme system, aryl hydrocarbon (benzo-[a]pyrene) hydroxylase, is highly inducible by substrate in monolayer cultures of the mouse thymus-spleen cell line, JLSV 5. The rise in enzyme activity is continuously dependent on protein synthesis and requires RNA synthesis during an initial 2-hour period. Selective inhibition of ribosomal RNA synthesis by actinomycin D before and during the presence of the inducer does not interfere with the increase in enzyme activity. Higher levels of actinomycin D ranging from 0.06 to 0.12 µg per ml inhibit both the increase in enzyme activity and the appearance of newly formed RNA in the cytoplasm. Similarly, suppression of ribosomal RNA synthesis by cycloheximide followed by the addition of high levels of actinomycin D and release of the block in protein synthesis does not prevent the increase in enzyme activity. Our results suggest that the early stages of enzyme induction require the synthesis of an RNA of the heterogeneous type whose formation, transport and expression as increased enzyme activity are independent of concomitant ribosomal RNA synthesis and transport to the cytoplasm.