A cancer epidemiologist recently said that "adduct measurement has so far been of little use to epidemiological research." This remark gives us a starting point for the discussion of the purposes of measuring macromolecule adducts that originate from electrophilic compounds or metabolites in humans and animals. Historically, methods for adduct monitoring were developed as a means of determining...

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a member of a class of compounds known as the heterocyclic amines (HCAs) that are formed in meat during cooking. It is a multi-organ carcinogen in rodents forms adducts and with DNA and protein. Although protein adducts are not thought to be involved in cancer development, they may be useful as internal dosimeters of PhIP exposure and bi...

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are heterocyclic amines formed during the cooking of meat and fish. Both are genotoxic in a number of test systems and are carcinogenic in rats and mice. Human exposure to these compounds via dietary sources has been estimated to be under 1 microg/kg body wt. per day, although most l...

In vivo 4-hydroxyamino[2-3H]quinoline 1-oxide-modified DNA and in vitro 4-acetoxyamino[2-3H]quinoline 1-oxide-modified DNA were enzymatically hydrolyzed, and the hydrolysates were analyzed by high-performance liquid chromatography. The two patterns were compared, and we showed that all of the high-performance liquid chromatography peaks which were recovered from in vivo-modified DNA were presen...

Sulfamethoxazole (SMX) and dapsone (4,4'-diaminodiphenylsulfone, DDS) are believed to mediate their adverse effects subsequent to bioactivation to their respective arylhydroxylamine and arylnitroso metabolites, resulting in covalent adduct formation with intracellular proteins. Various bioactivating enzymes, such as cytochromes P450 and myeloperoxidase, have been shown to be capable of catalyzi...

Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme which catalyzes the transacylation of the sn-2-fatty acid of lecithin to cholesterol, forming lysolecithin and cholesteryl ester. We have recently proposed a covalent catalytic mechanism for LCAT in which lecithin cleavage proceeds via the formation of a transition state tetrahedral adduct between the oxygen atom of the catalytic se...

Sulfamethoxazole (SMX) and dapsone (4,4 -diaminodiphenylsulfone, DDS) are believed to mediate their adverse effects subsequent to bioactivation to their respective arylhydroxylamine and arylnitroso metabolites, resulting in covalent adduct formation with intracellular proteins. Various bioactivating enzymes, such as cytochromes P450 and myeloperoxidase, have been shown to be capable of catalyzi...

The organometallic chemistry of 4d and 5d transition metals has been vastly dominated by closed-shell states. reactivity their metalloradical species is though remarkable, albeit yet poorly understood with limited mechanistic investigations available. In this work we report the synthesis characterization two mononuclear IrII species, including first dinitrogen adduct. These compounds activate d...

The curcumin is a well-known antioxidant that can scavenge free radicals efficiently. methyl radicals, generated by the metabolism of various genotoxic compounds such as hydrazines and peroxides, methylate sites in DNA. Herein, we have carried out density functional theory calculations to investigate scavenging activity toward ethyl through radical adduct formation (RAF), hydrogen atom transfer...

Screen printed electrodes were employed in a proof of concept determination of homocysteine and glutathione using electrochemically oxidized catechol via a 1,4-Michael addition reaction in the absence and presence of cysteine, and each other. Using cyclic voltammetry, the Michael reaction introduces a new adduct peak which is analytically useful in detecting thiols. The proposed procedure relie...