Cellular RNA/DNA

Covalent binding of chemical carcinogens to cellular macromolecules, DNA, RNA and protein, is wel1-accepted to be the first step in the tumor initiation process ( 1, 2). Most carcinogens, including polycyclic aromatic hydrocarbons (PAH), require metabolic activation to produce the ultimate electrophilic species which react with cellular macromolecules. Understanding the mechanisms of activation and the enzymes which catalyze them is critical to elucidating the tumor initiation process. 

Antigens usually are macromolecules that contain distinct antigenic sites or epitopes , which can be recognized and interact with the various components of the immune system. They can exist as individual molecules composed of synthetic organic chemicals, proteins, lipoproteins, glycoproteins, RNA, DNA, polysaccharides—or they may be parts of cellular structures (bacteria or fungi) or viruses (Male et al., 1987 Harlow and Lane, 1988). 

Cellular RNAs vary widely in their size, structure, and lifespan. The great majority of them are ribosomal RNA (rRNA), which in several forms is a structural and functional component of ribosomes (see p.250). Ribosomal RNA is produced from DNA by transcription in the nucleolus, and it is processed there and assembled with proteins to form ribosome subunits (see pp.208, 242). The bacterial 16S-rRNA shown in Fig. A, with 1542 nucleotides (nt), is a component of the small ribosomae subunit, while the much smaller 5S-rRNA (118 nt) is located in the large subunit. 

Pharmacology Metronidazole, a nitroimidazole, is active against various anaerobic bacteria and protozoa. It is believed to invoke cytotoxicity on the reduced nitro group in the bacterium cell. The liberated inactive end products are believed to target the RNA, DNA, or cellular proteins of the organisms. 

DNA is a linear polymer of deoxyribonucleotides in which the sequence of purine and pyrimidine bases encodes cellular RNA and protein molecules. 

Is it the case that all components of our cellular life are thermodynamically stable Of course not. We have around us many compounds in our biochemistry that are not under thermodynamic control - think of important compounds such as adenonine triphosphate (ATP), phospholipids, RNA, DNA, proteins. .. Nowadays, these compounds are formed thanks to the action of enzymes, which are often specialized for catalyzing the synthesis of products under kinetic control. 

Messenger RNA is only one of several classes of cellular RNA. Transfer RNAs serve as adapter molecules in protein synthesis covalently linked to an amino acid at one end, they pair with the mRNA in such a way that amino acids are joined to a growing polypeptide in the correct sequence. Ribosomal RNAs are components of ribosomes. There is also a wide variety of special-function RNAs, including some (called ribozymes) that have enzymatic activity. All the RNAs are considered in detail in Chapter 26. The diverse and often complex functions of these RNAs reflect a diversity of structure much richer than that observed in DNA molecules. 

Probes may also consist of DNA copied from mRNA. This is known as cDNA and is also widely used to determine indirectly the sequences of mRNA molecules. Messenger RNA may be isolated from the total cellular RNA by affinity chromatography on bound poly (dT) or poly (U). These materials selectively hold RNA with the poly (A) tails characteristic of most eukaryotic mRNA (see Chapter 28). Another source of mRNA is polyribosomes (polysomes), which are "reading" mRNA and actively making proteins. 

Hypothesis for how a retrovirus picks up a cellular protooncogene. The RNA-DNA cycle for retroviruses is shown in figure 26.25. The proviral DNA is believed to recombine the cellular DNA in such a way that it picks up a region of the cellular DNA containing a protooncogene. 

Longer term assessments of cell toxicity are highly dependent on the relevant toxic end point. They may include measurement of growth competence, apoptosis, and/or necrosis, incorporation of radioactive precursors into essential cellular constituents such as RNA, DNA, and protein and specialized cellular functions. Some examples of the use of cultured cell lines in the study of toxicity effects are shown in Table 2.1. 

Northern blotting follows much the same procedure as Southern blotting except that the sample analyzed by gel electrophoresis and then bound to the filter is RNA not DNA. Therefore the technique detects RNA molecules that are complementary to the DNA probe. If cellular RNA is electrophoresed, for example, a DNA probe for a specific mRNA could be used to detect whether that mRNA was present in the sample. The migration distance of the RNA in the gel would also allow estimation of its size. Note that Southern blotting (for DNA) obtained its name after its inventor (E. Southern) the name Northern blotting (for RNA) was devised later and is a geographical pun ... 

The two major products of the pathway are nicotinamide adenine dinucleotide (reduced form NADPH) and ribose 5-phosphate. Ribose 5-phosphate and its derivatives are components of important cellular molecules such as RNA, DNA, NAD+, flavine adenine dinucleotide (FAD), ATP and coenzyme A (CoA). NADPH is required for many biosynthetic pathways and particularly for synthesis of fatty acids and steroids. Hence the pathway is very active in tissues such as adipose tissue, mammary gland and the adrenal cortex. 

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