Enzymatic ribosylation of fluorescent 8-azapurine derivatives, like 8-azaguanine and 2,6-diamino-8-azapurine, with purine-nucleoside phosphorylase (PNP) as a catalyst, leads to N9, N8, and N7-ribosides. The final proportion of the products may be modulated by point mutations in the enzyme active site. As an example, ribosylation of the latter substrate by wild-type calf PNP gives N7- and N8-rib...

Ethylene oxide (EO) is widely used in the chemical industry and is also formed in humans through the metabolic oxidation of ethylene, generated during physiologic processes. EO is classified as a human carcinogen and is a direct acting alkylating agent, primarily forming N7-(2-hydroxyethyl)guanine (N7-HEG). To conduct accurate human risk assessments, it is vital to ascertain the relative contri...

Many xenobiotics exert their toxic effects through interaction with DNA in the cells of the exposed organism. This interaction may lead to the formation DNA adducts. Some of these may give rise to mutations that initiate cell transformation and, ultimately, the formation of tumors. Sensitive methods for determining DNA adducts are indispensable for the study of chemical mutagenesis and carcinog...

The macro acidity constants valid for aqueous solutions of several adenine, guanine, and hypoxanthine derivatives are summarized. It is shown how the application of the corresponding constants, e.g., for 7,9-dimethyladenine, allows a quantification of the intrinsic acidic properties of the (N1)H0/+ and (N7)H+ sites via micro acidity constants, and how to use this information for the calculation...

Ethylene oxide (EO) is widely used in the chemical industry and is also formed in humans through the metabolic oxidation of ethylene, generated during physiologic processes. EO is classified as a human carcinogen and is a direct acting alkylating agent, primarily forming N7-(2-hydroxyethyl)guanine (N7-HEG). To conduct accurate human risk assessments, it is vital to ascertain the relative contri...

An improved method is presented, based on gas chromatography-electron capture mass spectrometry (GC-EC-MS), for measuring N7-(2'-hydroxyethyl)guanine (N7-HEG) in DNA from an in vivo sample. The method was used to detect this adduct in amounts of human DNA ranging from 0.07 to 11.5 microg isolated from granulocytes. In this method, the DNA is spiked with a stable isotope internal standard (N7-HE...

Given the many roles proposed for Mg2+ in nucleic acids, it is essential to accurately determine their binding modes. Here, we surveyed the PDB to classify Mg2+ inner-sphere binding patterns to nucleobase imine N1/N3/N7 atoms. Among those, purine N7 atoms are considered to be the best nucleobase binding sites for divalent metals. Further, Mg2+ coordination to N7 has been implied in several ribo...

A problem that has hindered the study of the biological properties of certain DNA adducts, such as those that form at the N7 atoms of purines, is their extreme chemical lability. Conditions are described for the construction of a single-stranded genome containing the chemically and thermally labile 8,9-dihydro-8- (N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7-Gua) adduct, the major DNA adduct of th...

In solution, unsubstituted guanine (GH2) is in a tautomeric equilibrium between 1H,7H-keto and 1H,9H-keto forms. Upon coordination with (dien)Pt(II), N9-bound mononuclear complex is preferentially formed. With excess (dien)Pt(II), the dinuclear complex [{Pt(dien)}2(GH-N7,N9)]3+ is formed at basic pH. The X-ray crystal structure analysis of mononuclear complexes [Pt(dien)(GH2-N9)](ClO4)2 x 2.25 ...

Mycotoxins are toxic fungal metabolites which are structurally diverse, common contaminants of the ingredients of animal feed and human food. To date, mycotoxins with carcinogenic potency in experimental animal models include aflatoxins, sterigmatocystin, ochratoxin, fumonisins, zearalenone, and some Penicillium toxins. Most of these carcinogenic mycotoxins are genotoxic agents with the excepti...