Biomedical subjects

James Swenberg

Publications and source records attributed to James Swenberg.

3 recordsLinked to original sources

PubMed2006

Nonrandom AP site distribution in highly proliferative cells.

Reactive oxygen species (ROS) and the oxidative DNA damage they produce [e.g., 8-oxo-guanine and apurinic/apyrimidinic (AP) sites] have been linked to the pathogenesis of several age-related and chronic diseases. The basal number of AP sites measured in DNA by immuno-slot-blot analysis ranges from 70,000 to 100,000 per genome. We used electron microscopy to determine how AP sites were distributed in isolated DNA fibers from fresh calf thymus and HeLa cell cultures. We observed that AP sites were not equally distributed throughout all the fibers. A small percentage of the analyzed DNA fibers contained a disproportionate amount of the total AP sites in nonrandom groups of 10 to >30 closely spaced in a small region (e.g., 20 AP sites in a 6 kb length of DNA). This finding suggests that genomic sites may differ in their vulnerability to ROS damage, perhaps because of local chromatin structure. Nonrandom AP site formation also suggests that the detrimental effects of ROS in the development of disease may be related not simply to the total number of AP sites present but to how AP sites are distributed along a DNA fiber and, perhaps, to the genomic sites affected.

Amino Acid Sequence↗

PubMed2005

Personalized exposure assessment: promising approaches for human environmental health research.

New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. An ad hoc Committee on Environmental Exposure Technology Development was convened to identify new technologies and methods for deriving personalized exposure measurements for application to environmental health studies. The committee identified a "toolbox" of methods for measuring external (environmental) and internal (biologic) exposure and assessing human behaviors that influence the likelihood of exposure to environmental agents. The methods use environmental sensors, geographic information systems, biologic sensors, toxicogenomics, and body burden (biologic) measurements. We discuss each of the methods in relation to current use in human health research; specific gaps in the development, validation, and application of the methods are highlighted. We also present a conceptual framework for moving these technologies into use and acceptance by the scientific community. The framework focuses on understanding complex human diseases using an integrated approach to exposure assessment to define particular exposure-disease relationships and the interaction of genetic and environmental factors in disease occurrence. Improved methods for exposure assessment will result in better means of monitoring and targeting intervention and prevention programs.

Biomarkers↗

PubMed2003

The use of non-tumor data in cancer risk assessment: reflections on butadiene, vinyl chloride, and benzene.

The estimation and characterization of a cancer risk is grounded in the observation of tumors in humans and/or experimental animals. Increasingly, however, other kinds of data (non-tumor data) are finding application in cancer risk assessment. Metabolism and kinetics, adduct formation, genetic damage, mode of action, and biomarkers of exposure, susceptibility, and effects are examples. While these and other parameters have been studied for many important chemicals over the past 30-40 years, their use in risk assessments is more recent, and new insights and opportunities are continuing to unfold. To provide some perspective on this field, the ILSI Risk Science Institute asked a select working group to characterize the pertinent non-tumor data available for 1,3-butadiene, benzene, and vinyl chloride and to comment on the utility of these data in characterizing cancer risks. This paper presents the findings of that working group and concludes with 15 simple principles for the use of non-tumor data in cancer risk assessment.

Animals↗