DNA Damage by Chemicals

Many chemicals react with DNA, especially its bases, leading to various types of DNA damage. Increasing numbers of chemicals that can damage DNA are being 

3a DNA Damaging Chemicals without Metabolic Activation. These are chemical compounds that are reactive to DNA without further modification or metabolism in cells. Examples in this category are cisplatin compounds and simple alkylating agents. 

The major DNA lesions of cisplatin are intrastrand crosslinks, with cisplatin binding at the N7 position of purines. In vitro, reaction of ds-diamminedichloro-platinum (II) with DNA forms intrastrand crosslinks at the GG (65%), AG (25%), 

iii Simple Alkylating Agents. These are direct alkylating agents without the need for activation. They alkylate DNA by either the S,vl (Substitution, Nucleophilic, uni molecular) or the SN2 (Substitution, Nucleophilic, bjmolecular) mechanism. 

SW1 substitution involves an intermediate carbonium ion prior to its reaction with DNA, and proceeds with a first-order kinetics. The rate limiting step is the formation of the carbonium ion. SN2 substitution depends on both the alkylating agent and DNA. Thus, the reaction proceeds with a second-order kinetics. Multiple sites on 

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Establishment of minimum inhibitory concentrations (MICS) of various chemicals for growth of the Rec and Rec" strains in a liquid medium may give important quantitative information about production of bacteriocidal DNA damage by chemical mutagens. The following procedures are recommended. 

Blaskova M, Vyskocil V (2014) Simple electrochemical biosensor for comprehensive detection of DNA damage by chemical catcinogais. Chtan Listy 108(S4) S211-S215... 

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