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

• Published in: The Journal of biological chemistry Vol. 247; no. 15; pp. 4711 - 4717
• Main Authors: Wiebel, F J, Matthews, E J, Gelboin, H V
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 10-08-1972
• Subjects: Animals; Benz(a)Anthracenes - metabolism; Benzopyrenes; Biological Transport, Active - drug effects; Cell Line - enzymology; Cell Nucleus - analysis; Cycloheximide - pharmacology; Cytoplasm - analysis; Dactinomycin - pharmacology; DNA - analysis; Electrophoresis; Enzyme Induction - drug effects; Kinetics; Mice; Mixed Function Oxygenases - analysis; Mixed Function Oxygenases - biosynthesis; RNA - biosynthesis; RNA - isolation & purification; RNA - metabolism; RNA, Ribosomal - analysis; RNA, Ribosomal - biosynthesis; RNA, Transfer - analysis; RNA, Transfer - metabolism; Spleen; Thymus Gland; Tritium; Uridine - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)44971-5

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 heterogeneous 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.