The experimental data reviewed in this paper suggest that the inhibition of viral polypeptide chain initiation in IFN-treated cells involves the phosphorylation of eIF-2 alpha and intermediate factors (65K and 67K ribosomal proteins) by an IFN-induced dsRNA-dependent ribosomal kinase. However, the discrimination mechanism between viral and host cell mRNAs at the translational level remain to be elucidated, because the mechanism is very complex. IFN will induce, for example, preferential digestion of viral mRNAs by 2',5'-oligo A activated endoribonuclease, will impair tRNAs and elongation factors for the protein synthesis, and will decrease methylation of viral mRNAs, and they are involved in the discrimination mechanism at translational level. The activation of membrane-associated kinase activity by IFNs is very interesting because its among the earliest recognized biochemical events induced in cells and may play an important role in IFN-induced host or cell defense. Further studies focusing on the biochemical roles of the membrane-associated kinase in IFN-treated cells may provide evidence for understanding the biochemical mechanism of cell activation by IFNs.

Chick embryo cells respond to interferon by producing very high levels of 2-5A synthetase. From inhibitor studies, it appears that the response involves the controlled derepression of an interferon-inducible gene. Continuous interaction of the cells with interferon seems to be necessary to maintain maximal enzyme induction. Partial purification of the synthetase indicates that it is probably composed of a single polypeptide of 56,000 MW. Upon activation by binding to dsRNA, this polypeptide catalyzes a nucleotidyl transferase reaction in which 5'-AMP residues are transferred from ATP to the 2' position of appropriate acceptors. A number of naturally occurring small molecules (in addition to 2-5A itself) that can function as adenylate acceptors have been identified, but the physiological significance of these adenylylation reactions remain to be established.

The regulation of gene expression was studied, for the Escherichia coli rpoBC operon, which includes the genes, rpoB and rpoC, for the beta and beta subunits of RNA polymerase, and rplJ and rplL, for the two proteins, L10 and L7/12, of the 50S ribosome. The gene organization agrees well with the accumulated observations indicating the coordinate synthesis of RNA polymerase and ribosomes under various growth conditions for wild-type E. coli cells. On the other hand, the differential regulation of the two essential components observed under restrictive growth conditions, after addition of various drugs or with certain mutants, in particular those carrying mutations in the RNA polymerase genes, was found to take place through two novel regulation systems: The transcriptional termination at an internal attenuation site and the two autogenous and posttranscriptional controls, being specific for the two ribosomal protein genes and the two RNA polymerase subunit genes, respectively. The majority of the transcription initiated from the promoter rpoP beta terminates at an attenuator site between the promoter-proximal rplJL and the promoter-distal rpoBC genes. The frequency of the attenuation seems to control the relative level of RNA polymerase synthesis to that of ribosomes. The expression of rpoBC genes is subject to an autogenous regulation, in which both RNA polymerase holoenzyme and alpha 2 beta complex function as regulatory molecules with repressor activity. The autogenous regulation was found to operate at post-transcriptional step(s), probably at the level of translation. During the study on the regulation of RNA polymerase synthesis, we noticed that the rpoBC operon contained another autogenous regulation circuit, in which the synthesis of L10 and L7/12 was specifically repressed by the L10-L7/12 complex. Molecular mechanisms and physiological meanings of the novel regulations are discussed.

Chemicals are important and unavoidable parameters in the milieu of the laboratory animal used in biomedical research today. Examples of chemicals used include detergents and sanitizing agents. Detergents are used to remove dirt while sanitizing compounds, such as germicidal agents, decrease bacteria, fungi or viruses in the facility. The types used (that is, phenols, alcohols, oxidizing agents) depend upon the degree of cleanliness and the sanitizing properties desired and vary for germfree, specific pathogen-free and conventional animal facilities. Chemicals are routinely added to water to control bacteria in mouse facilities. Similarly, insecticides and pesticides are used to reduce the number of vermin in animal and feed rooms. Also, the bedding may contain chemicals (that is, cedrene and cedral in red cedar shavings). These and other chemicals in the vivarium may influence enzyme induction or inhibition, may result in increased or decreased toxicity, may alter the function or metabolism of organs and can thereby alter the outcome of animal experiments.

A diverse group of compounds inhibit the action of chemical carcinogens when administered prior to and/or simultaneously with the carcinogen. The inhibitors include naturally-occurring constituents of foods as well as synthetic compounds introduced into the environment. Three general mechanisms of inhibition exist. The first, illustrated by disulfiram inhibition of dimethylhydrazine-induced neoplasia of the large bowel, is the direct blocking of enzymatic activation of the carcinogen to its reactive ultimate carcinogenic form. The second mechanism of inhibition entails the stimulation of a coordinated detoxification response which results in increased activity of detoxifying enzymes in the microsomes and also the cytosol. At least two subdivisions of this response occur. One, for which butylated hydroxyanisole is a prototype, shows enhanced activity of some microsomal enzymes but not aryl hydrocarbon hydroxylase (AHH). However, it does have a rapidly active component which results in marked alteration of microsomal metabolism of benzo(a)pyrene. Another, for which a prototypical inhibitor is beta-naphthoflavone is characterized by induction of increased AHH activity. The third general mechanism of carcinogen inhibition entails the direct scavenging of reactive carcinogenic species by the inhibitor. Evidence supporting the psosibility that inhibitors play a role in the response of humans to carcinogens consists of three types. The first is the chemical diversity of the inhibitors and their actual occurrence in the environment. The second is the resposiveness of the detoxification systems, particularly those in the tissues of the major portals of entry, to the naturally-occurring or synthetic inhibitors. The third is a group of epidemiological studies which suggest that individuals consuming relatively large quantities of vegetables, a major source of naturally-occurring inhibitors, are at lower risk from gastrointestinal cancers.