Chemical lesions

Large doses of ultraviolet light can damage DNA. In humans this damage is confined to the skin, since, unlike x-rays, ultraviolet light is easily absorbed. The chemical lesion in this case is the formation of dimers between adjacent thymine residues on the same DNA strand. Unless corrected or removed, these dimers will stop DNA synthesis. 

PCR amplification of the single-stranded (ss) DNApool will result in multiple copies of a double-stranded DNA pool. Chemical lesions occurring during the chemical synthesis of the ss DNA pool, and the possibility that some sequences are more amplified than others during PCR procedures, may result in a limited pool size and predominance of sequence motifs in the random sequence (see below). Therefore it is necessary to sequence and analyze a small number of individual sequences of the random pool (2). 

We better understand the kinetics of spreading and the histological processes of destruction of the different ocular tissues. The pathophysiology of chemical lesions, in case of an ocular bum, wiU be strongly illustrated, thanks to new technologies which can bring the experimental evidence of the theories developed in the following chapters. 

The last consequence is that the chemical lesion is avoided or minimized. This facilitates the simplicity of the follow-up care in case of a secondary medical... 

E) Induction of irreversible changes in the structure of essential cell constituents as a result of exposure to the pharmacon. This implies a certain degree of chemical denaturation of these cell constituents indicated as chemical lesions 3,4 24-. ... 

Reversible interaction with the biological object results in pharmacodynamic effects which, in certain circumstances, may be undesired and therefore must be classed as toxic. Chemical lesions, with very few exceptions, are classed as definitely toxic. 

Regeneration processes, such as substitution of denaturated enzymes by enzyme synthesis and mechanisms for the repair of DNA, can sometimes render the effect of the chemical lesion transient. On the other hand, taking into account the essentially irreversible character of chemical lesions, there is a tendency for the effect to be cumulative. This accumulation is one of the main factors in the long-term toxicity of cancerogenic and mutagenic agents. 

The action radius of the reactive intermediates depends on their half-life and thus determines the localization of the chemical lesions. Products with highly reactive electrophilic groups will react with the water that is present in abundance. 

Species differences with regard to various toxic effects based on such chemical lesions and their localization in particular tissues are understandable on basis of species and tissue differences in the capacity of metabolizing pharmaca. The pharmacon under these circumstances acts as a toxogen (compare pharmacogen). It may be emphasized that, although the microsomal mixed-function oxidative system in the liver cells is generally considered to be a de-... 

As indicated in the introduction, chemical lesions are involved not only in carcinogenic and mutagenic actions, but also in allergic actions, tissue damage,... 

Baumgarten, H.G., and Lachenmeyer, L. Chemical lesioning of central monoamine axons by 5,6-dihydroxytryptamine and 5,7-dLihyd.ro s.y-try teimmQ. Adv Biochem Pharmacol 10 13-33, 1972. 

In a series of well-controlled studies, anti-sense oligonucleotides administered intraven-tricularly selectively inhibited dopamine type 2 receptor expression, dopamine type 2 receptor RNA levels, and behavioral effects in animals with chemical lesions. Controls included randomized oligonucleotides and the observation that no effects were observed on dopamine type I receptor or RNA levels (142-144). This laboratory also reported the selective reduction of dopamine type 1 receptor and RNA levels with the appropriate oligonucleotide (227). 

The likely basis for this selective biochemical effect on DNA synthesis came from the observation that the inhibition of DNA synthesis was persistent and progressive with time after removal of the drug. It is now clear, particularly by comparison with analogous effects produced by direct reacting agents such as mustard gas, that both effects are consistent with the view that the primary chemical lesion is in the DNA of the cell, which is then inhibited as a template for DNA replication. 

Numerous animal models exist for FID. A pattern of cell death similar to that observed in the disease progress can be induced by chemical lesion either with quinolinic acid (Beal et al., 1986) or 3-nitropropioinic acid (3-NP) (Beal et al., 1993). The discovery of the HD gene has further led... 

Recent studies utilizing microinjection of a neurotoxin to induce chemical lesions have implicated the pons (PoUacek et al. 2004), raphe nuclei (Jakus et al. 1998), and lateral tegmental field (Jakus et al. 2000) in the production of coughing. The microinjection method is best suited to the study of regions or nuclei of the brain... 

---