Cytotoxic affect

Figure 21.2 Conceptualized construction of an A-B subunit protein toxin (left). The B chain contains a binding region for docking onto cell surfaces, while the A chain contains a catalytic site that produces cytotoxic affects intracellularly. The two subunits are joined by a disulfide bond that is reductively cleaved at the cellular level to allow the A subunit to affect cell death. A molecular model of ricin is on the right.

DNA is very susceptible to radical-induced damage. The structural changes in DNA can cause cytotoxicity affecting the replication of DNA in vivo. 

British investigators (Haddow and Timmis 1951) synthesized and studied esters of the methanesulfonic acid. The most active derivative was the dimethylsulfonic ester of 1,4-butanedione, known as busulfan. Busulfan interacts with the thiol groups of proteins and amino acids some of its metabolites can alkylate the thiols of cysteine, peptides and proteins. Busulfan exerts selective cytotoxic activity in hematopoietic bone marrow cells and inhibits the formation of granulocytes and platelets. It slightly affects the lymphoid tissue. 

Perifascicular capillaries are closer to aggregates of antibody-secreting cells (B-lymphocytes) situated in perimysial connective tissue and therefore are most severely affected by antibody-dependent cytotoxic reactions. Immune-complex deposition occurs at a higher level in the vascular tree (i.e., at arteriolar level) and this may cause fluctuations in perfusion pressure. Perifascicular capillaries are most distal from the head of vascular pressure and therefore most likely to suffer from periodic anoxia. 

Mc2Sn(cap) and Et2Sn(cap) do not affect the embryonic development Bu2Sn(cap) and Bu2Sn(cap) exert toxic activity on C. intestinalis embryos in the early stages of development. This toxicity is concentration-dependent and is related to the lipophilic properties of the complexes. Cytotoxic... 

Changing the distribution of a drug can lead to toxic effects not described before. It is possible that after liposomal delivery high concentrations of drugs (e.g., cytotoxic drugs) inside macrophages affect these cells detrimentally (Poste and Kirsch, 1983). This results in toxic effects in liver, spleen, and bone marrow which were not previously associated with the use of these drugs. 

The poor dispersibility of CNTs in biological media can affect both the cytotoxicity [38] and the in vivo toxicity [39] of such nanomaterials. 

HU is an inhibitor of ribonucleotide reductase, a rate-limiting enzyme which catalyzes the conversion of ribonucleotides into deoxyribonucleotides. HU is thus a cytotoxic agent as it has the ability to inhibit DNA synthesis. Consequently, H U can affect only cells that are actively synthesizing DNA and, therefore, a drug of S-phase cell-cycle specific. Moreover, HU-mediated inhibition of ribonucleotide reductase is reversible, implying that the action of HU will exhibit a relatively straight forward concentration-time course dependence [2—4-]. 

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