Aromatic carbonyl compounds in combination with B(C(6)F(5))(3) are able to activate H(2) heterolytically. The reactivity of the carbonyl-B(C(6)F(5))(3) adduct is initiated by its thermal dissociation into components. After H(2) addition, aromatic carbonyl compounds convert into aryl-substituted methanes or alcohols.

Aromatic amines are bioactivated to electrophilic compounds that react with DNA, predominantly at the C8 position of guanine bases. This site is weakly nucleophilic and it has been proposed that the C8 adduct is the final product after initial N7-adduct formation. To consider this possibility, we reacted several C8-substituted guanine derivatives with N-acetoxy-2-aminofluorene, prepared in situ...

The methods applied for DNA adduct determination in humans have become more reliable. Yet there is a need to characterize the adducts studied better and when possible, to identify them with the help of the available standard compounds. Use of standard compounds also allows quantification of adduct levels. There is a lack of knowledge on the adduct levels and their half-lives in target and surro...

At the International Workshop on Genotoxicity Test Procedures (IWGTP) held in Washington, DC (March 25-26, 1999), a working group considered the uses of DNA adduct determination methods for testing compounds for genotoxicity. When a drug or chemical displays an unusual or inconsistent combination of positive and negative results in in vitro and in vivo genotoxicity assays and/or in carcinogenic...

Qualitative trapping profile of reactive metabolites arising from six structurally different compounds was tested with three different d-peptide isomers (Peptide 1, gly-tyr-pro-cys-pro-his-pro; Peptide 2, gly-tyr-pro-ala-pro-his-pro; Peptide 3, gly-tyr-arg-pro-cys-pro-his-lys-pro) and glutathione (GSH) using mouse and human liver microsomes as the biocatalyst. The test compounds were classified...

In natural-product drug discovery, finding new compounds is the main task, and thus fast dereplication of known compounds is essential. This is usually performed by manual liquid chromatography-ultraviolet (LC-UV) or visible light-mass spectroscopy (Vis-MS) interpretation of detected peaks, often assisted by automated identification of previously identified compounds. We used a 15 min high-perf...

DNA adducts derived from complex mixtures of polycyclic aromatic compounds emitted from tobacco smoke are compared to industrial pollution sources (e.g., coke ovens and aluminum smelters), smoky coal burning, and urban air pollution. Exposures to coke oven emissions and smoky coal, both potent rodent skin tumor initiators and lung carcinogens in humans, result in high levels of DNA adducts comp...

To assess the effects of chronic administration of tamoxifen (TAM) and toremifene (TOR) on genetic damage related to carcinogenesis, we measured DNA adduct formation by (32)P-postlabeling in liver, kidney, and uterus of Fischer rats given TAM or TOR in the diet for 18 months. TAM induced high levels of DNA adducts in the liver in a dose-dependent manner. The total adduct levels were 3000 +/- 87...

Part of our research program concentrates on the discovery of new bioactive compounds prepared either by total synthesis or molecular transformation of compounds with bioactivity profiles. In this work we have focused our interest on chemical transformations of the Diels-Alder adduct tricyclo[6.2.1.0(2,7)]undeca-4,9-dien-3,6-dione in order to obtain cage-like compounds and derivatives, followed...

Specific metabolites of estrogens, catechol estrogen-3,4-quinones, if produced in relatively large amounts, can become chemical carcinogens by reacting with DNA to form predominantly depurinating DNA adducts. Estradiol (E2)-3,4-quinone (Q) reacts with DNA to form predominantly the depurinating DNA adducts, 4-hydroxyestradiol (OHE2)-1-N3Ade and 4-OHE 2-1-N7Gua. The depurinating adducts induce mu...