Formation of thiazolidine-2,4-dicarboxylic acid, the L-cysteine-glyoxylate adduct, is the putative mechanism by which L-cysteine reduces hepatic oxalate production from glycollate [Bais, Rofe and Conyers (1991) J. Urol. 145, 1302-1305]. This was investigated in isolated rat hepatocytes by the simultaneous measurement of both adduct and oxalate formation. Different diastereoisomeric ratios of ci...

Chloronitrobenzenes (CNBs) are important intermediates for the production of dyes, pesticides, rubber chemicals, and drugs. 2CNB and 4CNB are possible human carcinogens. Therefore, it is important to develop methods to biomonitor people exposed to these occupational and environmental pollutants. We developed a method to determine hemoglobin (Hb) adducts of CNBs. Nitrobenzenes and the resulting ...

Administration of aflatoxin B1 (AFB1) to rats resulted in the urinary excretion of 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1. This is the major product formed by the interaction in vivo of AFB1 with rat liver nucleic acids. The adduct was isolated from urine by the combined use of preparative and analytical high-pressure liquid chromatography and was quantitated by measurement of absorban...

DNA polymerases must accurately replicate DNA to maintain genome integrity. Carcinogenic adducts, such as 2-aminofluorene (AF) and N-acetyl-2-aminofluorene (AAF), covalently bind DNA bases and promote mutagenesis near the adduct site. The mechanism by which carcinogenic adducts inhibit DNA synthesis and cause mutagenesis remains unclear. Here, we measure interactions between a DNA polymerase an...

Anthramycin-DNA adducts, produced in vitro by reaction of anthramycin with calf thymus DNA, have been shown to be stable only as long as the secondary structure of DNA is maintained. Denaturation either by heat or enzymatic degra dation of the DNA adduct, with DNase I and snake venom phosphodiesterase, leads to the release of significant amounts of the bound drug as unchanged anthramycin. These...

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...

During chemotherapy with a cisplatin-containing combination of drugs, 217 blood samples from 30 cancer patients were analyzed for the presence of the main cisplatin-DNA adduct cis-Pt(NH3)2d(pGpG) (Pt-GG). Cisplatin was administered during 3-h infusions on each of 5 consecutive days, resulting in increasing adduct levels which, on the average, were about twice as high after the fifth as after th...

Glycation of proteins leads to the formation of advanced glycation endproducts (AGEs) of diverse molecular structure and biological function. Serum albumin derivatives modified to minimal and high extents by methylglyoxal and glucose in vitro have been used in many studies as model AGE proteins. The early and advanced glycation adduct contents of these proteins were investigated using the 6-ami...

The variation in dietary exposure to acrylamide (AA) has been studied through measurement of hemoglobin adduct levels from AA, as a measurement of internal dose, in a sample from the blood bank of the Malmö Diet and Cancer Cohort (n=28,098). The blood donors are well characterised with regard to their food habits, and 142 individuals were selected to obtain highest possible variation in the add...