Hydrolysis and PAH Carcinogenicity

For a PAHDE to be carcinogenic it must have a reasonable lifetime to permit selective, specific and persisted interaction(s) with DNA. Activation near or at the target site is certainly the most effective means of generating potent carcinogens at a sufficiently high level. Still there are ample chances of detoxification either by its covalent binding to inhibitors or hydrolysis to inactive tetraols. 

Several questions arise regarding interrelationships between multiple reaction mechanisms of PAHDE s in the presence of nucleic acids. As in case of DNA binding, the solvolysis of BaPDE s, with or without DNA has been most thoroughly investigated over the last two decades. Hence, the ensuing discussions are focused on DNA-mediated hydrolysis of BaPDE, mentioning few other PAHDE s whenever relevant. 

When BaPDE reacts with DNA in aqueous solutions, quite a few pathways are possible  

A series of systematic studies on hydrolysis per se were undertaken by Sayer, Whalen, Islam, Jerina and others [147-150], The thrust of their research has been to identify the stereoelectronic, conformational and other incidental factors affecting the kinetics and product distribution in the solvolysis of various PAHDE s under diverse reaction conditions. The aim is, of course, elucidation of reaction mechanisms of PAHDE s in biological systems. Geacintov et al have conducted detailed investigations of reactions of BaPDE s with aqueous solutions of double stranded DNA as a function of temperature, pH and NaCl concentration at different levels of DNA contents [151]. 

A kinetic scheme is constructed to take into consideration different parameters which may influence noncovalent binding of BaPDE to DNA, the hydrolysis and covalent binding of the complexed DE molecules [151]. It is tacitly assumed that decay of free BaPDE molecules by hydrolysis is negligible i.e., kh k3, ki [DNA]. 

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