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...

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...

DNA repair genes have an important role in protecting individuals from cancer-causing agents. Polymorphisms in several DNA repair genes have been identified and individuals with non-dramatic reductions in the capacity to repair DNA damage are observed in the population, but the impact of specific genetic variants on repair phenotype and cancer risk has not yet been clarified. In 308 healthy Ita...

The formation of DNA adducts can lead to DNA replication errors and the potential for carcinogenesis. DNA adducts have been detected in prostate cells, but the distribution of adducts with respect to prostate cancer risk factors and histology is unknown. In a study of 130 Caucasian (n = 61) and African-American (n = 69) men with prostate cancer who underwent radical prostatectomy, we quantified...

The excision and persistence of covalent DNA adducts formed by A/-acetoxy-2-acetylaminofluorene (AAAF) were stud ied in human skin fibroblasts. The changes in adduct concen tration as a function of posttreatment incubation were meas ured in purified nucleosomal core DNA and in total nuclear DNA, and from these data the changes in adduct concentration in nucleosomal linker DNA were calculated. I...

Treatment of luminescence quenching upon adduct formation is often overlooked, leading to macroscopic errors. Here we provide a complete guide its treatment, for correct mechanism assessment and obtain reliable association constants.