ABSTRACT
It has been suggested that the measurement of DNA-protein cross-links (DPCs) may be of value in the assessment of an individual's exposure to specific environmental insults. For a biomarker to be reliable, its results should be consistent and specific. In the present study, the precision and specificity of the K(+)-SDS precipitation assay as a measurement for DPCs was assessed. Chinese hamster ovary (CHO) and human fibroblast cells were exposed to a number of diverse oxidative insults, whose concentrations ranged from physiological to super-physiological levels. Only super-physiological concentrations of the insults induced the formation of DPCs. Formaldehyde, chromate, vanadate, acetaldehyde, and copper were found to be the greatest inducers of DPC formation followed by manganese and iron. DPC induction was consistently higher in the CHO cells than in human fibroblast cells. While the K(+)-SDS assay may be of value as an indicator of cumulative DNA damage, its value as a biomarker for specific environmental insults may be limited.
Subject(s)
Acetaldehyde/toxicity , CHO Cells/drug effects , DNA-Binding Proteins/drug effects , Fibroblasts/drug effects , Formaldehyde/toxicity , Metals/toxicity , Animals , Biomarkers , CHO Cells/metabolism , Cells, Cultured , Chromates/toxicity , Copper/toxicity , Cricetinae , Cricetulus , DNA Damage , DNA-Binding Proteins/metabolism , Dose-Response Relationship, Drug , Environmental Exposure , Fibroblasts/metabolism , Humans , Iron/toxicity , Manganese Poisoning , Oxidation-Reduction , Oxidative Stress , Vanadates/toxicityABSTRACT
Human exposure to many pollutants occurs primarily through the ingestion of contaminated fish. In order to protect human health, regulatory agencies set limits on the levels of pollutants entering water bodies from point sources, thereby limiting the amount of pollutants that may be accumulated by fish. The limits, in the form of water quality criteria, are designed to correlate the concentration of a pollutant in a water body (and therefore the concentration accumulated by a fish) to the risks to humans. This type of model provides a reasonable way of controlling pollutants from point sources if the assumptions used in the model are realistic. However, the risk assessment formula currently used for developing water quality criteria only considers those pollutants in the water column available to fish through bioconcentration across the gills (freely dissolved pollutants). For strongly hydrophobic pollutants like dioxin, an extremely small fraction of the total amount is freely dissolved; most dioxin is sorbed to organic matter and is ingested by fish. A new model for developing criteria is presented here that takes into account the environmental fate of dioxin (predominantly in the sorbed state in the environment) and that fish accumulate dioxin by ingestion, rather than bioconcentration.
